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B.R. Nahata Smriti Sansthan
International Journal of
Pharmaceutical and Biological Archive
Volume 11 / Issue 2 / Apr-Jun-2020
B.R. Nahata Smriti Sansthan International Journal of Pharmaceutical and Biological Archive
Printed and published by Mr. Rahul Nahata on behalf of B.R. Nahata Smriti Sansthan and printed
at Fun and Art, 29, Nagar Palika Complex, Gandhi Chouraha, Mandsaur - 458001 [M.P.] and
published at Nahata Chouraha, Station Road, Mandsaur - 458001 [M.P.] editor Mr. M.A.Naidu.
ISSN: 2582-6050[Online]

B. R. Nahata Smriti Sansthan International Journal of Pharmaceutical and Biological Archive • Apr-Jun 2020 • 11 (2) | i
B. R. Nahata Smriti Sansthan International Journal of Pharmaceutical and Biological Archive
EDITORIAL BOARD TEAM
Dr. Manish Vyas
Associate Professor, School of Pharmaceutical Sciences,
Lovely Professional University, Phagwara, Punjab, India
E-mail: vymanish@gmail.com
Liliya Logoyda
Associate Professor, Department of Pharmaceutical Chemistry,
I. Ya. Horbachevsky Ternopil State Medical University,
Ukraine
E-mail: logojda@tdmu.edu.ua
Dr. Mushtak Talib Salih Al-Ouqaili
Vice-Chancellor for Scientific affairs, University of Anbar-
Iraq, Member in American Society for Microbiology, National
Secretary of IAESTE-Iraq, Iraq
E-mail: ph.dr.mushtak_72@uoanbar.edu.iq
Dr. Wan Mohd Nuzul Hakimi W Salleh
Department of Chemistry, Faculty of Science and
Mathematics, Universiti Pendidikan Sultan Idris (UPSI),
35900 Tanjung Malim, Perak, Malaysia
E-mail: wmnhakimi@fsmt.upsi.edu.my
Prof. Vd. KRC Reddy
Director, Pharmacopoeia Commission for Indian Medicine &
Homoeopathy, Ministry of AYUSH, Govt. of India, Ghaziabad
E-mail: drkrcreddybhu@yahoo.co.in
Dr. Mahendran Sekar
Associate Professor, Faculty of Pharmacy and Health
Sciences, Universiti Kuala Lumpur Royal College of Medicine
Perak, Malaysia
E-mail: mahendransekar_05@yahoo.co.in
Dr. H. N. K. AL-Salman
Professor, Department of Pharmaceutical Chemistry, College
of Pharmacy, University of Basrah, Iraq
E-mail: hsennaserh@yahoo.com
Dr. Gopal Lal Khatik
M.S. Pharm., Ph.D., Associate Professor, Department of
Pharmaceutical Chemistry, Lovely Professional University,
Phagwara, Punjab, India
E-mail: gopal_niper@rediffmail.com
Dr. Raghavendra L. Hallur
The Medical School (FMB), São Paulo State University (UN-
ESP), Botucatu- 18618-687, Sao Paulo State, Brazil
E-mail: raghu.biogem@gmail.com
Dr. Dev Nath Singh Gautam
MD (Ay.), Ph.D., Associate Professor, Department of Rasa
Shastra, Faculty of Ayurveda, Institute of Medical Sciences,
Banaras Hindu University, Varanasi, Uttar Pradesh, India
E-mail: drdnsgautam@gmail.com
EDITORIAL BOARD
Dr. M. A. Naidu
B.R. Nahata College of Pharmacy, Mandsaur, M.P., India
E-mail: editor@brnsspublicationhub.org
EDITOR-IN-CHIEF

B. R. Nahata Smriti Sansthan International Journal of Pharmaceutical and Biological Archive • Apr-Jun 2020 • 11 (2) | ii
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B. R. Nahata Smriti Sansthan International Journal of Pharmaceutical and Biological Archive • Apr-Jun 2020 • 11 (2) | iii
Contents
REVIEW ARTICLE
Novel Antihypertensive Drug Used in Clinical Practice: A Review
Sanjay Bais, Sarfaraz Kazi, Sajid Shaikh��65
RESEARCH ARTICLES
Assessment of Knowledge Regarding Antibiotic Use, its Resistance, and Future Consequences
among Higher Secondary Students in Private Schools of Kathmandu Valley
Satish Kumar Deo, Paridhi Sharma, Sushma Deo, Shikha Yadav, Sujaya Gupta��71
New Derivatives of (E)-3-(5-((substitutedphenylamino)methyl)-1,3,4-thiadiazol-2-yl)-2-styryl
quinazolin-4(3H)-one: Searching for New Antifungal and Antibacterial Agents
Aditya Sahu, Arun Patel, Himanshu B. Sahoo��76
Effects of Noise Stress on Body Weight and Adrenal Gland Weight of Male Wistar Rats
Ravinder Kr Mehra, Mahesh Prasad, Dinesh Kr Sharma, Ravinder Kr Mehra��91
Qualitative Evaluation and Wound Healing Potential of Selected Medicinal Plants by Excision
Wound Model
Neelesh Kumar, Arun Patel, Himanshu B. Sahoo��99

© 2020, IJPBA. All Rights Reserved 65
Available Online at www.ijpba.info
International Journal of Pharmaceutical Biological Archives 2020; 11(2):65-70
ISSN 2582 – 6050
REVIEW ARTICLE
Novel Antihypertensive Drug Used in Clinical Practice: A Review
Sanjay Bais1
*, Sarfaraz Kazi2
, Sajid Shaikh3
1
Department of Quality Assurance, Fabtech College of Pharmacy, Sangola, Solapur, Maharashtra, India, 2
Department
of Pharmacy, Shri Jagdishprasad Jhabarmal Tibrewala University, Jhunjhunu, Rajasthan, India, 3
Department of
Pharmacology, Vedprakash Patil College of Pharmacy, Georai Tanda, Aurangabad, Maharashtra, India
Received: 01 February 2020; Revised: 01 March 2020; Accepted: 01 April 2020
ABSTRACT
Introduction: Blood pressure (BP) control continues to be important in reducing cardiovascular risk, along
with the modification of other cardiovascular risk factors, especially cholesterol level. Lifestyle modification
to reduce BP may control Stage 1 hypertension. Drug treatment should be based on evidence of improved
outcomes and individualized account for the patient age, race, and quality of life. BP varies from minute
to minute and is influenced by measurement technique, time of day, emotion, pain, discomfort, hydration,
temperature, exercise, posture, and drugs. Purpose of Review: In this review, we examine how synthetic novel
drugs involved in the management of hypertension not only in the wider population but also within special
population groups such as the elderly, pregnant women, and those with a trial fibrillation. Conclusion: The
extensivesyntheticworkcarriedoutshowsthatsomemoleculesareveryeffectivelymanagingthehypertension
in all ages of patients. Summary: We have made an attempt in reviewing the literature on 1,2 pyrazoline
derivatives for their medicinal uses with the help of chemical abstract, journals, and internet surfing.
Keywords: Blood pressure, clinical management, hypertension, synthetics drugs
*Corresponding Author:
Dr. Sanjay Bais
E-mail: sanjaybais1968@gmail.com
INTRODUCTION
Blood pressure (BP) control continues to be
important in reducing cardiovascular risk, along
with the modification of other cardiovascular risk
factors, especially cholesterol level. Lifestyle
modification to reduce BP may control Stage 1
hypertension. Drug treatment should be based on
evidence of improved outcomes and individualized
account for patient age, race, and quality of life.
Although the number of cardiovascular deaths has
decreased over the past 25 years, achieving long-
term control of hypertension in millions of patients
remains an important objective. BP varies from
minute to minute and is influenced by measurement
technique, time of day, emotion, pain, discomfort,
hydration, temperature, exercise, posture, and
drugs. The dividing line between normal BP and
hypertension is arbitrary.[1,2]
According to the
Joint National Committee VI, hypertension is
when the diastolic BPs measurement is 90 mm
Hg or higher, and systolic BPs measurement is
consistently 140 mm Hg.[3]
Hypertension remains
one of the largest unmet medical needs in the
21st
century, especially when one considers that
hypertension is the potent of future debilitating
cardiovascular disease.[1]
The interrelation of a
number of regulatory factors to control BP and
tissue perfusion was first described by page in
1949. According to this concept, tissue perfusion/
pressure/resistance are interdependent on factors
designated chemical, reactivity, volume, vascular
caliber, viscosity, cardiac output, elasticity,
and multifactorial derangement of normal
equilibrium.[4]
The baroreceptors, mainly in the
walls of the aorta and the internal carotid arteries,
act on rapidly adjust to changes in pressure (stretch)
response time in seconds. This is accomplished by
activation of afferent nerves from the baroreceptors

Bais, et al.: Novel anti-hypertensive drug used in clinical practice: A review
IJPBA/Apr-Jun-2020/Vol 11/Issue 2 66
to the brain stem centers and modulation of efferent
sympathetic nerve activity of peripheral blood
vessels (norepinephrine release), to kidney(remain
release) to the heart (acetylcholine release).
SYMPTOMS OF HYPERTENSION[5,6]
Hypertension often has no symptoms. The only
way to detect it is to check it regularly, such as
headache, nosebleeds, blurred vision, palpitation,
dizziness, and tinnitus (ringing in the ear).
CAUSES OF HYPERTENSION[3,7-9]
The most common of them are as follows: Obesity,
alcohol intake, cigarette smoking, high sodium
intake, anxiety, diabetes, endocrine disorders such
as adrenal disorders, thyroid disorders, and Cushing
syndrome, and medications such as appetite
suppressants, corticosteroids, and birth control pills.
DIFFERENT TYPES OF HYPERTENSION
(1) Primary hypertension:[10]
Individuals typically
suffer primary hypertension as a result of poor
lifestyle habits, while this type of hypertension
accounts for most of the cases diagnosed by
doctors. While medication may be required,
dietary changes, stress management, and physical
activity are essential elements of treatment.
(2) Secondary hypertension:[11]
Secondary
hypertension is the symptom of an underlying
medical condition such as kidney disease,
problems with the liver, congestive heart failure,
stress, sleep apnea, or endocrine disorders such
as hyperthyroidism or Cushing’s syndrome,
which produces elevated levels of hormones.
Renal artery stenosis is a frequent cause of
secondary hypertension. Treatment of secondary
hypertension involves controlling the underlying
medical condition or disease in addition to
prescribing antihypertensive drugs. (3) Alcohol-
induced hypertension:[12]
Heavy drinking of
alcohol may be one of the most common causes
of secondary hypertension. (4) Isolated systolic
hypertension:[13]
Isolated systolic hypertension
occurs in people as they grow older. The build-up
of plaque in the arteries makes it more difficult for
blood to flow through. Treating the elderly with
diuretics not only decreases the risk of developing
the cardiovascular disease but may also reduce
the risk of dementia and related depression.
(5) Pregnancy-induced hypertension:[14]
It
begins to suffer from hypertension after the 20th
week of pregnancy. In the majority of cases,
these women are overweight or obese. Women
who are diagnosed with pregnancy-induced
hypertension are at greater risk of preeclampsia
during pregnancy. Symptoms may include
headache, dizziness, swelling of the hands and
face, nausea, vomiting, and pain in the abdomen.
(6) Medication-induced hypertension:[15]
Non-
steroidal anti-inflammatory drugs, decongestants,
and weight loss supplements are common
OTC drugs that can cause an increase in BP.
Corticosteroids, immunosuppressive, and cancer
drugs are among the prescription medications,
for which high BP can be a side effect. These
drugs constrict blood vessels and can cause
kidney problems. (7) Malignant hypertension:[16]
Malignant hypertension is considered to be a
medical emergency as the BP can suddenly rise to
a dangerous level.[17-21]
MECHANISM OF HYPERTENSION
Three theories have been proposed to explain
this:[22]
• The inability of the kidneys to excrete sodium,
resulting in natriuretic factors such as atrial
natriuretic factor being secreted to promote salt
excretion with the side effect of raising total
peripheral resistance
• An overactive renin–angiotensin system (RAS)
leads to vasoconstriction
and retention of
sodiumandwater.Theincreasein bloodvolume
plus vasoconstriction leads to hypertension
• An overactive sympathetic nervous system,
leading to increased stress responses.
RAS
The RAS or the renin-angiotensin-aldosterone
system (RAAS) is a hormone system that regulates

ANTIHYPERTENSIVE DRUGS
History of treatment of hypertension[26]
hypertension and its drug therapy has been
remarkably improved in the past 50 years. Different
classes of drugs have received prominence with the
passage of time in this period. Before 1950, hardly
any effective and tolerated antihypertensive agent
was available. Veratrum and sodium thiocyanate
could lower BP but were toxic and difficult to
use. The ganglionic blockers developed in the
1950s were effective but inconvenient. The
therapeutic potential of hydralazine could not
be tapped fully because of marked side effects
when it was used alone. Guanethidine introduced
in 1961, was an improvement in ganglionic
blockers. The antihypertensives of the 1960–70s
were methyldopa, β blockers and diuretics were
consolidated in the 1970s and selective α-blocker
prazosin broke new grounds. The antihypertensives
of the 1980–1990s are angiotensin-II converting
enzyme inhibitors (ACE) and calcium channel
blockers. Angiotensin II antagonists are the
latest antihypertensives.[27,28]
Diuretics help the
kidneys eliminate excess salt and water from the
body’s tissues and blood.[27]
For example, loop
diuretics such as bumetanide, ethacrynic acid,
furosemide, torsemide, and thiazide diuretics are
epitizide, hydrochlorothiazide, and chlorothiazide
bendroflumethiazide. Thiazide-like diuretics
are indapamide and chlorthalidone metolazone,
potassium-sparing diuretics are amiloride,
triamterene, and spironolactone. Despite lowering
BP and water (fluid) balance.[23]
Aldosterone causes
the tubules of the kidneys to increase the reabsorption
of sodium and water into the blood. This increases
the volume of fluid in the body, which also increases
BP.[23,24]
These drugs are one of the main ways to
control high BP (hypertension), heart failure, kidney
failure, and the harmful effects of diabetes.[25]

reserpine. Angiotensin II receptor antagonists,
also known as angiotensin receptor blockers, AT1
-
receptor antagonists, or sartans, are a group of
pharmaceuticals which modulate the RAAS. Their
main use is in hypertension (high BP), diabetic
nephropathy (kidney damage due to diabetes), and
congestive heart failure [Figure 1].[28,29]
DRUG COMPARISON AND
PHARMACOKINETICS[30]
The mean BP reduction achieved with losartan in
a dosage of 50–150 mg once daily is 5.5–10.5 mm
Hg for systolic pressure and 3.5–7.5 mm Hg for
diastolicpressure.[31]
Ahydrochlorothiazide-losartan
combination (Hyzaar) is also available. This
combinationcontains12.5mgofhydrochlorothiazide
and 50 mg of losartan.[32]
Candesartan cilexetil has
been shown to be effective for the treatment of
hypertension [Table 1]. The affinity of candesartan
for the AT1
receptor is more than 10,000 times
greater than its affinity for the AT2
receptor. With
Valsartan taken in a dosage of 80–320 mg once
daily, the mean reduction in diastolic BP is 6–9 mm
Hg. Studies have shown that valsartan is as effective
as enalapril, lisinopril, and amlodipine in the
treatment of mild-to-moderate hypertension.[33,34]
Figure 1: Factors affecting arterial pressure[22]
BP, alpha-blockers have a significantly poorer
endpoint and are no longer recommended as a
first-line choice in the treatment of hypertension.[27]
Calciumchannelblockers:Calciumchannelblockers
block the entry of calcium into muscle cells in
artery walls like dihydropyridine are amlodipine,
felodipine, isradipine, lercanidipine, nicardipine,
nifedipine, nimodipine, nitrendipine and non-
dihydropyridines:diltiazem, and verapamil. ACE
inhibitors inhibit the activity of ACE, an enzyme
responsible for the conversion of angiotensin I
into angiotensin II, a potent vasoconstrictor,[28]
for
example, captopril, enalapril, fosinopril, lisinopril,
perindopril, quinapril, ramipril, trandolapril, and
benazepril. Angiotensin II receptor antagonists
work by antagonizing the activation of angiotensin
receptors are candesartan, eprosartan, irbesartan,
losartan, olmesartan, telmisartan, and valsartan.
Vasodilators act directly on the smooth muscle
of arteries to relax their walls, so blood can move
more easily through them; they are only used in
hypertensive emergencies
or when other drugs
have failed and even so are rarely given alone.[28]
Sodium nitroprusside, a very potent, short-acting
vasodilator, is most commonly used for the quick,
temporary reduction of BP in emergencies (such
as malignant hypertension or aortic dissection).[27]
Hydralazine and its derivatives are also used in the
treatment of severe hypertension, although they
shouldbeavoidedinemergencies.[27,28]
Centralalpha
agonists lower BP by stimulating alpha-receptors
in the brain which open peripheral arteries easing
blood flow,[28]
for example, clonidine, guanabenz,
methyldopa, moxonidine. Some adrenergic
neuron blockers are used for the most resistant
forms of hypertension, such as guanethidine and
Table 1: Drug comparison and pharmacokinetics of angiotensin II blocking agent[30]
Drug Trade
name
Biological
half-life (h)
Protein
binding (%)
Bioavailability
(%)
Renal/hepatic
clearance (%)
Food
effect
Daily dosage
(mg)
Losartan Cozaar 2 h 98.7 33 10/90 Minimal 50–100 mg
EXP 3174 6–9 h 99.8 – 50/50 – –
Candesartan Atacand 9h 99 15 60/40 No 4–32 mg
Valsartan Diovan 6 h 95 25 30/70 No 80–320 mg
Irbesartan Avapro 11–15 h 90–95 70 1/99 No 150–300 mg
Telmisartan Micardis 24 h 99 42–58 1/99 No 40–80 mg
Eprosartan Teveten 5 h 98 13 30/70 No 400–800 mg
Olmesartan Benicar 14–16 h 99 29 40/60 No 10–40 mg

The affinity of the valsartan for the AT1 receptor is
about 20,000 times greater than its affinity for AT2
receptor. In comparison, the affinity of losartan for
AT1 receptor is about 1000 times greater than its
affinity for AT2 receptors.[31]
Irbesartan is a safe
and effective angiotensin II receptor antagonist
with an affinity for the AT1 receptor that is more
than 8500 times greater than its affinity for AT2
receptor.[35]
Non-linear pharmacokinetics yield
a greater than proportional increase in plasma
telmisartan concentration with increasing dosage.
It is a newly synthesized molecule which requires
a very high daily dose as compared to other drugs
of this class of around 400–500 mg.[36]
It is orally
administered in the form of olmesartan medoxomil
in combination with hydrochlorothiazide. Twenty
milligram or 40 mg olmesartan medoxomil is
combined with 12.5 mg hydrochlorothiazide and 40
mg with 25 mg hydrochlorothiazide.[33-40]
Adverse
effects:[41,42]
Orthostatic hypotension, dyspepsia,
decreased hemoglobin level, insomnia, renal
impairment, pharyngitis or nasal congestion, and
hyperkalemia.
CONCLUSION
The present work which was undertaken is novel
work on the synthesis of various medicinal
derivatives. We have made an attempt in reviewing
the literature on drug for their medicinal uses
with the help of chemical abstract, Journals and
internet surfing. The drugs were found to be non-
toxic and could be synthesized in good yield. The
active drugs were taken as lead for the treatment
of hypertension. The present work is an attempt
in this direction and the efforts have proved to be
fruitful and promising.
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Chemistry. 5th
ed. Philadelphia, PA: Lippincott Williams
and Wilkins; 2002. p. 533-60.
29. Hoeper MM, Barberà JA, Channick RN, Hassoun PM,
Lang IM, Manes A, et al. Diagnosis, assessment, and
treatment of non-pulmonary arterial hypertension
pulmonary hypertension. J Am Coll Cardiol
2009;54:S85-96.
30. Nelson M. Drug treatment of elevated blood pressure.
Aust Prescr 2010;33:108-12.
31. Gradman AH, Arcuri KE, Goldberg AL, Ikeda LS,
Nelson EB, Snavely DB, et al. A randomized placebo-
controlled, double-blind, parallel study of various doses
of Losartan potassium compared with enalapril maleate
in patients with essential hypertension. Hypertension
1995;25:1345-50.
32.
Rhodes CJ, Davidson A, Gibbs JS, Wharton J,
Wilkins MR. Therapeutic targets in pulmonary arterial
hypertension. Pharmacol Ther 2009;121:69-88.
33. Oparil S, Dyke S, Harris F, Kief J, James D, Hester A,
et al. The efficacy and safety of Valsartan compared
with placebo in the treatment of patients with essential
hypertension. Clin Ther 1996;18:797-809.
34. Holwerda NJ, Fogari R,Angeli P, Porcellati C, Hereng C,
et al. Valsartan, a new angiotensin II antagonist for the
treatment of essential hypertension: Efficacy and safety
compared with placebo and enalapril. J Hypertems
1996;14:1147-51.
35. Weir MR, Elkins M, Liss C, Vreenak AJ, Barr E,
Edelman JM. Efficacy, tolerability and quality of life
of Losartan, alone or with hydrochlorothiazide, versus
Nifedipine GITS in patients with essential hypertension.
Clin Ther 1996;18:411-28.
36. Severe P. Candesartan citexitil: A new, long acting,
effective angiotensin II Type 1 receptor blocker. J Hum
Hypertens 1997;11:S91-5.
37. Kassler-Taub K, John TL, Elliott W, Ruddy T, Alder E.
Comparative efficacy of two angiotensin II receptor
antagonists Irbesartan and Losartan in mild-to-moderate
hypertension. Am J Hypertens 1998;11:445-53.
38. Micardis. Psckage Insert Ridgefielld Conn. Ingelheim
am Rhein: Boehringer Ingelhim Pharmaceuticals, Inc.;
1998.
39. Bottorff MB, Tenero DM. Pharmacokinetics of
eprosartaninhealthysubjects,patientswithhypertension,
and special populations. Pharmacotherapy 1999;
19:73S-8S.
40. Gardner SF, Franks AM. Olmesartan medoximil:
The seventh angiotensin receptor antagonist. Ann
Pharmacother 2003;37:99-105.
41. Wexler RR, Greenlee WJ, Irvin JD, Goldberg MR,
Prendergast K, Smith RD, et al. Nonpeptide angiotensin
II receptor antagonists: The next generation in
antihypertensive therapy. J Med Chem 1996;39:625-56.
42.
Müller-Nordhorn J, Willich SN. Angiotensin II
antagonists in the treatment of hypertension effective
and efficient? Herz 2003;28:733-7.

ISSN 2582 – 6050
RESEARCH ARTICLE
Assessment of Knowledge Regarding Antibiotic Use, its Resistance, and Future
Consequences among Higher Secondary Students in Private Schools of Kathmandu
Valley
Satish Kumar Deo1
*, Paridhi Sharma2
, Sushma Deo3
, Shikha Yadav4
, Sujaya Gupta5
1
Department of Clinical Pharmacology, Maharajgunj Medical Campus, Institute of Medicine, Tribhuvan
University, Kathmandu, Nepal, 2
Department of Dental Surgery, Kantipur Dental College, Kathmandu, Nepal,
3
Department of Clinical Pharmacology, Janaki Medical College, Janakpur, Nepal, 4
Alliance against Antimicrobial
Resistance, Kathmandu, Nepal, 5
Department of Periodontics, Kathmandu Medical College, Kathmandu, Nepal
Received: 01 January 2020; Revised: 25 February 2020; Accepted: 01 April 2020
ABSTRACT
Antimicrobial resistance poses a growing threat to public health, as infections from resistant strains of
microbial become increasingly difficult and expensive to treat, resulting in prolonged illness and greater
risk of death. A cross-sectional descriptive study was done among 471 higher secondary level students
of private schools in Kathmandu Valley. Data were collected from Grade 11 and 12 non-science faculty
students through self-administered questionnaires. Half (50.5%) of the students gave correct response by
saying that antibiotic kills bacteria and 49.1% said that it is for fever. Majority (93.0%) of them said that it
should be taken with water. Regarding the response on when to stop taking antibiotic, 46.9% said correctly
by saying when all prescribed medicines are taken whereas and 40.8% said that after feeling better. More
than half (58.8%) of the students had not heard about antibiotic resistance, whereas those who have heard
among them 24% of students said that they had heard from doctor and nurses and 21.8% from family
member and friends. Nearly one-third (32.7%) of students knew that antibiotic resistance occurs using
antibiotic when they are not necessary. Regarding the response on consequences of antibiotic resistance,
more than one-third (38.2%) of students gave correct answer. Nearly half of the students have lack of
knowledge about antibiotic. Thus, it is imperative to create awareness among students by introducing a
specific course on antibiotic in the 9th
and 10th
grade core curriculum to prevent antibiotic resistance and
its consequences.
Keywords: Antibiotic resistance, antibiotic use, antibiotic, future consequences
INTRODUCTION
Antibiotics resistance in many ways a very
frightening issues and finding solution to problem
caused by these infections can be a daunting task.[1]
By examining the ways, antibiotic resistance can
be minimized and controlled and hope for a
healthier and safer future.[2]
There is an urgent need
for more investment in research and development
Dr. Satish Kumar Deo
E-mail: satish.deo@iom.edu.np
for antibiotic-resistant infections including TB;
otherwise, we will be forced back to a time when
people feared common infections and risked their
lives from minor surgery.[3]
Antimicrobial resistance (AMR) is one of the most
serious health threats. Infections from resistant
bacteria are now too common, and some pathogens
have even become resistant to multiple types or
classes of antibiotics. When the first-line and then
second-line antibiotic treatment options are limited
by resistance or are unavailable, health-care
providers are forced to use antibiotics that may
be more toxic to the patient and frequently more

Deo, et al.: Knowledge regarding antibiotic use, its resistance, and Future consequences among higher secondary students
expensive and less effective. Even when alternative
treatments exist, research has shown that patients
with resistant infections are often much more likely
to die, and survivors have significantly longer
hospital stays, delayed recuperation, and long-term
disability.[4]
Antibiotic resistance is accelerated by
the misuse and overuse of antibiotics, as well as
poor infection prevention and control.[5]
If the appropriate steps are not put forward
immediately, the arrival of post antibiotic era is
inevitable, when the patient will die even with
the infections which are considered minor. In
Nepal, the AMR surveillance is not up to the
mark, since its commencement. There is an urgent
need of collaboration between the department of
health services (Ministry of Health), department
of livestock services (Ministry of Livestock
Development), and Ministry of Population
and Environment for having joint surveillance
program.[6]
A very few research work has been done in Nepal
about antibiotic resistance and future consequences
among non-medical students. Numerous people use
antibiotics in simple cold and cough and sometimes
they do not complete the dose of antibiotics.[7]
Hence, this study would be an important reference
for determining the scope of the problem which
will be essential for formulating and monitoring an
effective response to antibiotic use and its problem
of resistance. Hence, the purpose of this study is
to assess awareness of higher secondary students
regarding antibiotic use and the threat or future
consequences that antibiotic resistance poses and to
encourage immediate action to address the threat.
MATERIALS AND METHODS
A cross-sectional descriptive study was done in
November 2017 among 471 higher secondary level
students of private schools in Kathmandu Valley.
Among 185 private higher secondary schools of
Kathmandu valley, five schools were selected
whose management were supportive. From each
school, all Grade 11 and 12 students of non-science
group were selected for this study. Convenience
sampling technique was used. Data were collected
from Grade 11 and 12 non-science faculty
students through self-administered questionnaires.
Descriptive statistics were used to find out the
knowledge level of the students.
Data collection tool
Semi-structured questionnaire was developed
after reviewing the related literature to obtain the
information regarding knowledge of antibiotic
use, its resistance, and future consequences and
questions were divided into two parts:
• Section A: Questions related to the
sociodemographic variables
• Section B: Questions related to the knowledge
of antibiotic use, its resistance, and future
consequences.
The adequacy and accuracy of content of the
instrument were established by designing the
questionnaire based on the study objectives, taking
help from the previous literature and studies.
Instrument was formed in English language and
opinion of the language expert was obtained for
comprehensibility and simplicity of language. The
reliability of the instrument was established by
pre-testing the instrument on 10% Grade 11 and
12 students in the similar but not the same setting.
Table 1 shows demographic data included age,
gender, educational status, and socioeconomic
status. Each question (apart from those included in
thedemographicdatasection)wasinaformatoffive
possible answers (accepting only one right answer),
according to the 5-point Likert scale: 1 = strongly
agree, 2 = agree, 3 = uncertain, 4 = disagree, and
5 = disagree strongly or 1 = always, 2 = most of
the times, 3 = often, 4 = sometimes, and 5 = never.
Data collection procedure
Written permission was taken from concerned
private higher secondary schools before the study.
The schedule for data collection was prepared
according to the suitable date and time (after
lunch i.e., 1 pm) by consulting each school’s
administration. The students of Grade 11 and 12
of each school were kept in their own separate
classrooms. Researchers gave their introduction,
stated the objective of the data collection, and

provided information on how to fill the self-
administered questionnaire (they were also told
that they were free to ask in between questionnaire
filling if any difficulty arose) to the respective
classroom students. Informed verbal consent was
taken from students before data collection. The
students were assured of the confidentiality of the
information given by them. The students were told
that they are allowed to refuse to participate in
the study at any time if they wish. Then, the self-
administered questionnaires were distributed to the
students. It took nearly ½ h to fill the questionnaire,
and then, the students were thanked for their
kind cooperation and providing the time for data
collection. It took 5 days to collect data from five
schools as each day was allocated for one school.
Data analysis
The collected data were coded and entered in
computer software package (SPSS 21.0) program.
The data analysis was done using descriptive
statistics. Findings were interpreted through
percentage and frequency tables to show the
students’ knowledge level.
Ethical considerations
Ethical approval was obtained from research
committee of TU, IOM. Permission was obtained
from the concerned authority of higher secondary
colleges. Purpose of the study was explained
and written consent was taken from the students.
Information obtained was used for the study
purpose. The students were allowed to refuse to
participate in the study at any time they want.
RESULTS AND DISCUSSION
In this study, the mean age of the students was 17.19
years. About 52% were male and 71.1% were from
Grade 12. Half (50.5%) of the students gave correct
response by saying that antibiotic kills bacteria and
49.1% said that it is for fever. Majority (93.0%) of
them said that it should be taken with water. About
47% of students said that headache is the side effect
of antibiotic while 30.6% said vomiting, whereas
10.5% were unaware of the side effects. Regarding
the response on when to stop taking antibiotic,
46.9% said correctly by saying when all prescribed
medicines are taken whereas and 40.8% said that
after feeling better. More than half (58.8%) of the
students had not heard about antibiotic resistance,
whereas those who have heard among them 24% of
students said that they had heard from doctor and
nurses and 21.8% from family member and friends.
Table 1: Semi-structured questionnaire sociodemographic
information
Ø Age (in years)
Ø Gender
Ø Grade
Ø Stream
Ø Father’s income
1.
Questions about knowledge, attitude, and practice about antibiotic
resistance, its use, and correlation with one health concept
2. Antibiotics are powerful medicines that are used to kill bacteria?
3. Antibiotics are used to treat cough and cold?
4.
Vomiting, headache, diarrhea, abdominal pain, etc., are the common
side effects of antibiotics?
5.
Do you imagine the future without antibiotics to be dangerous for
living beings?
6.
Do you think you should stop taking antibiotics when you feel better
once you’ve begun a treatment?
7. We die if we get an antibiotic resistant infection?
8. You often take antibiotics no matter what the illness is?
9.
Have you heard of any of these terms such as antimicrobial resistance,
antibiotic resistance, drug resistance, or antimicrobial resistance?
10. Is the efficacy better if antibiotics are newer and more costly?
11.
Do you think frequent use of antibiotics will decrease efficacy of
treatment when using the antibiotics again?
12. There is abuse of antibiotics at present?
13.
Abuse of antibiotics has become the main cause leading to bacterial
resistance?
14. Antibiotic resistance affects you and your family’s health?
15.
Is there a need to establish course on rational use of antibiotics at
high school level?
16. Scientists can produce new antibiotics for resistant bacteria?
17.
Parents and medical health professionals should be informed about
judicious antibiotic use?
18.
Should we ask the physician about the necessity of prescribing
antibiotics?
19.
Would you change your physician if he/she didn’t prescribe
antibiotics?
20.
Do you think transfer of resistant bacteria from animal to human or
vice versa is possible?
21.
Do you agree with the fact that low dose antibiotic should be
condemned because it favors antibiotic resistance?
22. Do you agree that antibiotic residues are found on food supply?

Nearly one-third (32.7%) of students knew that
antibiotic resistance occurs using antibiotic when
they are not necessary. Regarding the response on
consequences of antibiotic resistance, more than
one-third (38.2%) of students gave correct answer.
According to Santimano and Foxcroft (2016)
survey of high school students in Goa, India,
overall, antibiotic knowledge was poor, with 49%
of students either wrongly thinking or unclear
that bacteria cause colds/flu. Most (82%) students
thought that antibiotics killed harmful viruses,
35% thought that antibiotics do not kill harmful
bacteria, and 79% thought that antibiotics do not
kill harmless bacteria. Most (67%) were unaware
of the problem of antibiotic resistance.[8]
According to antibiotic resistance, multicountry
public awareness survey conducted in the WHO
12 member states – face-to-face street interview
was taken in the 9772 respondents – reported
that antibiotic use is higher in the lower income
countries included in the survey. About 25% of
respondents across the 12 countries included in the
survey think that it is acceptable to use antibiotics
that were given to friend, family member, as long
as they were used to treat the same illness. About
43% think that it is acceptable to buy the same
antibiotics or request these from a doctor, if they
are sick and antibiotics helped them get better
when they had the same symptoms before. About
32% of respondents think that they should stop
taking antibiotics when they feel better, not when
they have taken all of them as directed.[9]
Another study done on knowledge and attitude
toward antibiotic use and resistance – a latent
class analysis of a Swedish population-based
sample mentioned that antibiotic treatment is a
pre-requisite for modern healthcare. For this study,
questionnaire was sent to by post in 2013–25,000
randomly selected individuals aged 18–74 living in
Sweden and overall response rate was 57% out of
which 94% knew that bacteria become resistance to
antibiotics, 70% answered the questions regarding
side effects correctly, and even fewer 50% of
respondents correctly to questions regarding how
antibiotics resistance can spread. A minority 12%
answered correctly “no” to the statements – people
can become resistant to antibiotics. Moreover, they
have concluded that people with lower education
and the elderly are especially in need of improved
knowledge about antibiotic use and resistance.[10]
Similar study conducted on antibiotic use: A
cross-sectional survey assessing the knowledge,
attitudes, and practices among students of a school
of medicine in Italy among medical, dental, and
nursing health-care professionals students of the
school of Medicine where 1050 were interviewed
and concluded that around 20% of the sample stated
that antibiotics are appropriate for viral infections
and 15% of the students that they stop taking those
drugs when symptoms decrease. Results of the
multivariate analyses showed that females were
more likely than males to take antibiotics only
when prescribed (OR 1.43, 95% CI 1.04–1.98).
Interestingly, students with a relative working in
a health-related field, as well as those who took
at least one course of antibiotics in the past year,
had a lower probability of taking those drugs only
under prescription (OR = 0.69 95% CI: 0.49–0.97
and OR = 0.38 95% CI: 0.27–0.53, respectively).
Moreover, the study has concluded that health-care
profession students do not practice what they know.
Since those students will be a behavioral model for
citizens and patients, it is important to generate
more awareness around this issue throughout
their studies and would be advisable to introduce
a specific course and training on antibiotics in the
core curriculum of the School of Medicine.[11]
A
cross-sectional survey of public knowledge and
attitudes with regard to antibiotics in Poland: Did
the European antibiotic awareness day campaigns
change attitudes? was conducted among general
public in Poland in five waves between 2009 and
2011 embracing a total of 5004 respondents showed
that 3% of the respondents purchased an antibiotic
without a prescription. Approximately 40% of the
respondents expected prescriptions for an antibiotic
against the flu. The vast majority knew antibiotics
kill bacteria (80%), but at the same time, 60% of
respondents believed that antibiotic kills viruses.[12]
CONCLUSION
Nearly half of the students have lack of knowledge
about antibiotic. Thus, it is imperative to create
awareness among students by introducing a specific

course on antibiotic in the 11th
and 12th
grade core
curriculum to prevent antibiotic resistance and its
consequences.
LIMITATION OF STUDY
The study was conducted on higher secondary level
students of non-science group. Only non-medical
students were studied.
REFERENCES
1. Basnyat B, Pokharel P, Dixit S, Giri S. Antibiotic
use, its resistance in Nepal and recommendations for
action: A situation analysis. J Nepal Health Res Counc
2015;13:102-11.
2. Centre for Disease Control and Prevention. Antibiotic/
Antimicrobial Resitance; 2018. Available from: https://
www.cdc.gov/drugresistance/index.html. [Last accessed
on 2018 Jan 26].
3. Centers for Disease Control and Prevention. Antibiotic
Resistance Threats in the United States; 2013. Available
from: http://www-cdc-govdrugresistancethreat-report-
2013pdf. [Last accessed on 2018 Jan 26].
4. Deo SK, Rijal S, Tulza KC. Public awareness regarding
the use and resistance of antibiotics; a cross sectional
study among Nepalese adults in Kathmandu Valley. J
Kathmandu Med Coll 2016;6:96-101.
5. Frieden T. Antibiotic Resistance Threats in the United
States. U. S. Department of Health and Human Services
Centers for Disease Control and Prevention; 2013.
Available from: https://www.cdc.gov/drugresistance/pdf/
ar-threats-2013-508.pdf. [Last accessed on 2018 Jan 28].
6. Huang Y, Gu J, Zhang M, Ren Z, Yang W, Chen Y.
Knowledge, attitude and pratice of antibiotics; A
questionaire study among 2500 Chinese students. 2013.
London: Biomed Central the Open Access Publisher.
7. Khan AK, Banu G, Resma KK. Antibiotic resistance and
usage-a survey on the knowledge, attitude, perceptions
and practices among the medical students of a southern
Indian teaching hospital. J Clin Diagn Res 2013;7:1613-6.
8. King S, Exley J, Taylor J, Kruithof K, Larkin J,
Pardal M. Antimicrobial Stewardship-The Effectiveness
Of Educational Interventions To Change Risk-Related
Behaviors In The General Population: A Systematic
Review; 2015. Available from: http://www.rand.org/
content/dam/rand/pubs/research_reports/rr1000/rr1066/
rand_rr1066.pdf. [Last accessed on 2018 Jan 28].
9. KotwaniA, Wattal C, Joshi PC, Holloway K. Knowledge
and perception on antibiotic use and resistance among
high school students and teacher in New Delhi-India.
Indian J Pharm 2016;48:365-71.
10. Mazinbka B, Struzycks I, Hryniewicz W. Surveys of
public knowledge and attitudes with regard to antibiotics
in Poland. PLoS J 2017;12:e0172146.
11. Nordqvist C. Antibiotics All You Need To Know,
Medical News Today; 2017. Available from: https://
www.medicalnewstoday.com/articles/10278.php. [Last
accessed on 2018 Jan 28].
12. Richardson LA. Understanding and overcoming
antibiotic resistance. PLoS Biol 2017;15:e2003775.

ISSN 2582 – 6050
RESEARCH ARTICLE
New Derivatives of (E)-3-(5-((substitutedphenylamino)methyl)-1,3,4-thiadiazol-2-
yl)-2-styryl quinazolin-4(3H)-one: Searching for New Antifungal and Antibacterial
Agents
Aditya Sahu*, Arun Patel, Himanshu B. Sahoo
Department of Pharmacy, RKDF College of Pharmacy, SRK University, Bhopal, Madhya Pradesh, India
Received: 01 February 2020; Revised: 25 March 2020; Accepted: 10 April 2020
ABSTRACT
Objective: The objective of the paper was to evaluate the antifungal and antibacterial potential of new
derivatives of ((E)-3-(5-((substitutedphenylamino)methyl)-1,3,4-thiadiazol-2-yl)-2-styryl quinazolin-4(3H)-
one. Materials and Methods: Various syntheses of (E)-3-(5-(substitutedaminomethyl)-1,3,4-thiadiazol-2-
yl)-2-styrylquinazolin-4(3H)-one derivatives have been synthesized by reacting 2-substituted benzoxazin-4-
one with (E)-2-(4-Substituedstyryl)-4H-benzo[d] [1,3]oxazin-4-one. All synthesized compounds have been
characterized by the infrared, 1HNMR, and mass spectral analysis. Proposed compounds have been evaluated
for antifungal and antibacterial activity. The antimicrobial activity of synthesized compounds (QNM-1 to QNM-
15) has been carried through the serial dilution method. For bacterial screening, bacterial species were taken
includes Staphylococcus aureus (MTCC-96), Bacillus subtilis (MTCC-441), Pseudomonas aeruginosa (MTCC-
424), and Escherichia coli (MTCC-40). Norfloxacin (1-Ethyl-6-fluoro-1,4,dihydro-4-oxo-7-(1-piperazinyl)-3-
quinoline carboxylic acid) was used as the standard drug for antibacterial study. For antifungal screening, the
following fungal species were used includes Aspergillus niger (MTCC-281), Candida albicans (MTCC-227),
and Fusarium oxysporum (MTCC-284). Clotrimazole was selected as a standard drug for antifungal study.
Results and Discussion: QNM-1, QNM-2, QNM-3, QNM-5, QNM-7, QNM-9, QNM-12, QNM-14, and
QNM-15 were the most active compounds [Table 1] in the synthesized series which were active against both
Gram-positive and Gram-negative organisms by the antibacterial screening. In the case of antibacterial activity,
the presence of electronegative group (Cl, Br, F, and NO2
) at both R may enhance the activity when they are
p-substituted,butthecompoundsQNM-6(R1=-C6
H5
Br(o);Ar=-C6
H5
),QNM-10(R1
= -C6
H5
F(o);Ar=-C6
H5
F),
QNM-11 (R1 =-C6
H5
NO2
(p); Ar=-C6
H5
F), and QNM-4 (R1 =-C6
H5
F (m); Ar=-C6
H5
) with given substitution
may result in diminishing the activity. In case of antifungal activity, compounds QNM-1, QNM-5, QNM-7,
QNM-9, QNM-11, QNM-12, QNM-14, and QNM-15 were the most active compounds in the synthesized series
which were active against both Gram-positive and Gram-negative organisms. In that series, compounds QNM-
14, QNM-11, QNM-5, and QNM-7 have shown the highest activity. Compounds QNM-3, QNM-6, QNM-10,
and QNM-13 have the least active. This result has also concluded that o-substituted compounds, i.e., -C6
H5
Cl(o),
-C6
H5
Cl (m), -C6
H5
Br(o), -C6
H5
F (o), -C6
H5
F (p) at R1
position my resulted in diminishing or lower the activity.
Keywords: Antibacterial, antifungal, clotrimazole, norfloxacin, quinazoline, serial dilution method
Aditya Sahu
E-mail: adityasahurock93@gmail.com
INTRODUCTION
The searching and finding of a new compound
with therapeutic potentials numerous approaches
explained and explored by the scientist, and this
research resulted in the form of dosages that help
to cure diseases as well as to maintain health. The
development of new drugs has been responsible for
decreasing human morbidity and mortality more
than any other scientific endeavor. These products
have dramatically improved the quality of life

Sahu, et al.: Quinazolin-4(3H)-one derivatives: Search for new antifungal and antibacterial agent
across all ages.[1]
They can prevent illness or when
illness occurs, speed recovery, reduces hospital
stays, and decreases the need for surgery.To explore
new drugs, many hurdles and difficulties were
arise and to solve this many rational approach has
been developed, i.e., many chemical mediators or
enzymes or specific receptor have been identified
that play a crucial role in the cure, treatment and to
defining the pathological condition. This helps to
identify the diseases and their treatment. Candidate
drugs designed and synthesized partly on the basis
of such known mediators, hormones, metabolites,
or substrates.[2]
Quinazoline is an aromatic heterocyclic with a
bi-cyclic structure consisting of two fused six-
member aromatic rings, a benzene ring, and
pyrimidine ring. Quinazoline is a compound made
up of two fused six-member aromatic rings, a
benzene ring, and a pyrimidine ring. Quinazoline is
a fused bicyclic compound earlier known as benzo-
1,3-diazine was first prepared in the laboratory by
Gabriell. Depending on the position of the keto or
oxo group, these compounds may be classified into
three types including 4(3H)-quinazolinone, 2(1H)
quinazolinone, and 2,4 (1H,3H)-quinazolinedione,
of the three quinazolinone structures 4(3H)-
quinazolinone are most prevalent, either as
intermediates or as natural products in many
proposed biosynthetic pathways.
Quinazolinone is a potent hypnotic agent
and has been reported to exhibit analgesic,
anesthetic, antifungal,[3,4]
antibacterial,[5]
anticancer, anticonvulsant, antihypertensive,
anti-inflammatory, antioxidant, diuretic, muscle
relaxant, sedative, anti-hepatitis-A virus, and
tranquilizer properties. The 4(3H)-quinazoline
and its derivatives have been reported to exhibit
anticonvulsant, antimicrobial,[6,7]
sedative,
tranquilizer,antiviral,[8]
analgesic,[9]
antibacterial,[10]
anesthetic, anticancer, antimalarial,[11]
diuretic,
antihypertensive, anti-inflammatory, and muscle
relaxant properties. 2-Methyl-3-o-tolyl-4(3H)-
quinazolinone (Methaqualone) is the most
frequently prescribed quinazolinone derivative as
a safe sedative-hypnotic and anticonvulsant drug.
A literature survey revealed that the presence of
substituted aromatic ring at 3rd
position and methyl/
phenyl group at 2nd
position of 4(3H)-quinazolinone
are necessary requirements for the antibacterial
activity. This hypothesis encourages us to build the
modificationofquinazolinoneat2nd
and3rd
position.
In this paper, 15 compounds have been synthesized
using different substitution of benzaldehyde at R1
position and -o,-m,-p substitution at Ar position
Table 1: Antibacterial activity of the synthesized compounds
Codes Ar R1
R2
Antibacterial activity MIC in µg/ml
Staphylococcus
aureus (MTCC-96)
Bacillus subtilis
(MTCC-441)
Pseudomonas aeruginosa
(MTCC-424)
Escherichia coli
(MTCC-40)
QNM-1 -C6
H5
-C6
H5
H 6.14±0.24 12.34±0.14 9.20±1.08 9.14±0.26
QNM-2 -C6
H5
-C6
H5
Cl (o) H 6.16 ±0.63 16.46±0.66 11.88±0.56 10.68±0.66
QNM-3 -C6
H5
-C6
H5
Cl (m) H 5.44±0.36 14.66±0.46 10.28±1.6 11.04±0.36
QNM-4 -C6
H5
-C6
H5
F (m) H 8.18 ±0.64 14.64±0.88 9.22±0.66 9.44±0.66
QNM-5 -C6
H5
-C6
H5
NO2
(p) H 4.42±0.40 7.32±0.16 8.23 ±1.02 9.13 ±0.20
QNM-6 -C6
H5
-C6
H5
Br(o) H 7.22±0.75 15.20±0.80 12.36±0.44 10.22±0.88
QNM-7 -C6
H5
Br -C6
H5
Br (p) H 4.40±0.22 8.62±1.80 8.44 ±0.66 8.44 ±0.25
QNM-8 -C6
H5
Br -C6
H5
F (p) H 5.83±0.26 10.43±0.22 9.42 ±0.25 11.6 ±0.90
QNM-9 -C6
H5
Br -C6
H5
NO2
(p) H 4.46±0.12 6.40±0.80 8.73 ±1.86 8.58±0.98
QNM-10 -C6
H5
F -C6
H5
F (o) H 9.12±0.22 15.22±0.26 9.34 ±0.82 12.28±0.36
QNM-11 -C6
H5
F -C6
H5
NO2
(p) H 8.16±0.70 13.45±0.20 8.56±0.29 8.58±0.86
QNM-12 -C6
H5
CH3
-C6
H5
Cl (p) H 4.40±0.28 8.28±0.60 9.28±0.76 8.54±0.86
QNM-13 -C6
H5
CH3
-C6
H5
F H 6.45±1.60 15.45±0.80 9.62 ±0.22 8.67±0.80
QNM-14 -C6
H5
CH3
-C6
H5
NO2
H 4.58±0.34 8.68±0.38 8.65±1.64 9.36±0.26
QNM-15 -C6
H5
CH3
-C6
H5
Br H 4.62±0.24 9.60±0.48 9.26±1.66 8.24±0.40
Norfloxacin 4.36±0.20 14.48±0.72 8.48±0.96 8.49±0.28

in the 4(3H)-quinazolinone has design to improve
the antifungal and antibacterial activity. The
objective of the papers was to design, synthesize,
and evaluation of synthesized compounds for
antifungal and antibacterial activity.
MATERIALS AND METHODS
2-chloroacetyl chloride, thiosemicarbazide, and
formaldehyde were purchased from Sigma-
Aldrich, New Delhi. Substituted anilines (Aniline,
o-fluoro aniline, m-fluoro aniline, p-chloro aniline,
o-chloro aniline, m-chloro aniline, o-bromo aniline,
m-bromo aniline, p-bromo aniline, and p-nitro
aniline) were purchased from HiMedia. Acetic
anhydride, di-methyl formamide, glacial acetic
acid substituted, and benzaldehyde (Benzaldehyde,
p- fluorobenzaldehyde, p-Bromobenzaldehyde,
and p-Tolualdehyde) were purchased from CDH
(Chemical Drug House), New Delhi, India. The
chemical used for experimental work was synthetic
grade. The melting points of the synthesized
compounds were determined in open glass
capillaries. Infrared (IR) spectra were recorded on
ALPHA(Bruker)FouriertransformIRspectrometer.
Elemental analysis was performed, and found
values were within 0.4% of theoretical values. 13C
NMR spectra were recorded on Bruker Avance 400
spectrophotometer at 400 MHz, 5 mm multi-nuclear
inverse probe head, low, and high-temperature
facility, and HRMAS accessory. Mass spectra were
recorded using Mass Spectrometers Jeol SX-102
(Fast atom bombardment [FAB]) by ESI.
Chemistry
The synthesis of (E)-3-(5-
(substitutedaminomethyl)-1,3,4-thiadiazol-2-yl)-
2-styrylquinazolin-4(3H)-one is accompanied in
Figure 1.
Present synthesis comprises
1. Synthesis of 1,3,4-thiadiazole
2. Synthesis of (E)-3-(5-(((4-Substitutedphenyl)
amino)methyl)-1,3,4-thiadiazol-2-yl)-2-
styrylquinazolin-4(3H)-one.
Figure 1: Schematic representation of synthesis-I and scheme-II

SYNTHESIS-I
Synthesis of 1,3,4-thiadiazole
Step 1: Synthesis of 5-(chloromethyl)-1,3,4-
thiadiazol-2-amine
In that reaction, substituted amino thiadiazole [3]
was prepared by the conventional method by the
following procedure: In this reaction, 2-chloroacetyl
chloride[2](0.1M)andthiosemicarbazide[1](0.1M)
weremixedandrefluxedwithConc.sulfuricacidfor
2½ h. When the reaction is completed, the reaction
mixture was cooled in ice bath and neutralized
with the ammonia solution (2.5%). The reaction
was monitored by the thin-layer chromatography
(TLC) method.[12]
The solid product thus obtained
was filtration and re-crystallize using 75% ethanol.
The product is characterized by 1HNMR (6.99 ppm
N-H; 4.62 ppm CH2
), and ultraviolet (UV)-spectral
analysis. The compounds were shown peak at 280
nm by UV spectroscopic analysis.
Step 2: Synthesis of 5-(substituted-amino methyl)-
1,3,4-thiadiazol-2-amine
In that reaction, 5-(chloromethyl)-1,3,4-thiadiazol-
2-amine [3] (0.1M) was taken in round bottom flask,
andformaldehydewasdissolvedinmethanol(3.0ml)
and was added dropwise with continuous stirring.[13]
The resulting mixture was stirred for half an hour
to complete the mixing. To this reaction mixture,
methanol solution of Aniline, o-fluoro aniline,
m-fluoro aniline, p-chloro aniline, o-chloro aniline,
m-chloro aniline, o-bromo aniline, m-bromo aniline,
p-bromo aniline, and p-nitro aniline (0.1M) [4] was
mixed and reflux for 2 h at 65–70°C. Then, after the
reaction mixture was cool at room temperature and
solution poured in cold water. The solidification of
compounds arise, and obtained solid was filtered
and washed with hot distilled water.[14]
The obtained
solid product was air-dried for further synthesis. The
obtained compound [5] was characterized by IR,
1HNMR and was found consistent with an expected
structure. The IR data of 3270.5 (N-H str.); 3082.5
(Ar. C-H); 1515.3 (C=N str.); 642.5 (C-S str.); and
1466.9 (N=O asym. str.) confirm the compound
N-((5-amino-1,3,4-thiadiazol-2-yl)methyl)
nitramide. This compounds further confirmed by
the 1HNMR (167 C2
-1,3,4-thiadiazole, 56 ppm
CH2
-NH). TLC has been performed each and every
step to confirm the completion of the reaction.
SYNTHESIS-II
Synthesis of (E)-3-(5-(((4-Substitutedphenyl)
styrylquinazolin-4(3H)-one
Step 1: Synthesis of 2-methyl-4H-benzo[d][1,3]
oxazin-4-one
In this reaction, anthranilic acid [6] (0.01 M) was
refluxed under the anhydrous condition for 4 h
using acetic anhydride as a solvent the remaining
un-reacted acetic anhydride was distilled off to get
product N-acetyl anthranillic acid. Then, N-acetyl
anthranillic acid was further refluxed with acetic
anhydride, under anhydrous condition for 4 h to
obtain the solid mass of 2-methyl benzoxazin-4-
one [7]. The products were dried and recrystallized
from petroleum ether.[15]
Reaction was monitored
by the TLC for the completion of the reaction. The
compounds 7 (2-methyl benzoxazine-4-one) was
characterized by 1H-NMR spectra (7.09-8.128
(δ ppm) = m, 4H (Ar); 2.511 (δ ppm ) = s, 3H,
CH3
). The 2-methyl benzoxazine-4-one was also
confirmed by the IR analysis, IR peak shows at N-H
str. (primary amine 3580 cm−1
), Ar-CH (3200 cm−1
).
Step 2: Synthesis of 3-(5-((Substitutedamino)methyl)-
1,3,4-thiadiazol-2-yl)-2 methyl quina zolin-4(3H)-one
In that reaction, 2-methyl-4H-benzo[d][1,3]oxazin-4-
one [7] (0.1 M) and obtained compounds [5] (0.1 M)
was suspended in glacial acetic acid[7]
and refluxed
for 4 h. After completion of reaction, the reaction
mixture was cooled at room temperature, and then
it was poured into crushed ice and kept overnight in
the refrigerator.[16]
The obtained solid product [8] was
filtered, washed with cold water and recrystallized
from hot ethanol (75%). The synthesis was monitored
by the TLC for the completion of the reaction.
Step 3: Synthesis of (E)-3-(5-(((4-Substitutedphenyl)
styrylquinazolin-4(3H)-one
In that reaction, equimolar quantity of
compound [8] (0.2 M) was taken in round bottom

flask, benzaldehyde and substituted benzaldehyde
(p- fluorobenzaldehyde; p-Bromobenzaldehyde/p-
Tolualdehyde) were dissolved in glacial acetic
acid (0.2 M)and refluxed at 130–140°C for
2
h by the addition of anhydrous zinc chloride
(0.1 g). After, reaction completion, the mixture
was washed with cold water to dissolve un-
reacted zinc chloride.[17]
The obtained solid residue
after filtration was washed with cold ethanol.
Purification of the synthesized compounds [9]
was done by dissolving the compounds in the
minimum quantity of dimethylformamide (DMF)
and then added this solution to distilled water. This
synthesis was monitored by the TLC to confirm the
completion of the reaction.
Antimicrobial activity
Evaluation of antimicrobial activity
Evaluation of the antimicrobial activity has
been carried through the serial dilution method.
Minimum inhibitory concentration (MIC) was
determined by the serial dilution method.[18]
Antibacterial screening of the synthesized compounds
(QNM-1 to QNM-15)
For the bacterial screening of the synthesized
compounds (QNM-1 to QNM-15), the
following bacterial species were taken includes
Staphylococcus aureus (MTCC-96);[19]
Bacillus
subtilis (MTCC-441);[20]
Pseudomonas aeruginosa
(MTCC-424); and Escherichia coli (MTCC-40).
Norfloxacin(1-Ethyl-6-fluoro-1,4,dihydro-4-oxo-
7-(1-piperazinyl)-3-quinolinecarboxylic acid) was
used as the standard drug for antibacterial study. It
is active against Gram-positive and Gram-negative
bacteria both. It acts by inhibiting the subunit of
DNAgyrase, which is essential for the reproduction
of bacterial DNA.[21]
Preparation of Solution of Standard Drug
A stock solution of norfloxacin (1 mg/ml) was
prepared in DMF (N,N-DMF). Further dilutions
were made accordingly using the same solvent as
per the requirements.
Preparation of solution of the synthesized compounds
A stock solution of each synthesized compound
(1 mg/ml) was made in DMF. Further dilutions
were made as above according to requirements.
Measurement of activity
Determination of MIC
The serial dilution method has been used for the
determination of MIC. A set of “8” sterilized test
tubes were taken, and different solutions were
transferred aseptically to each test tube as per the
quantities given below:
Test tube no. 6, 7, and 8 was controls. Test tube 6
containednoinhibitorthatconfirmedtheculturewas
viable and no solvent effect. Test tube 7 contained
neither inhibitor nor organism, which confirmed
the sterility of the culture, test tube 8 contained a
high concentration of inhibitor but no organism to
detect the precipitation caused by the interaction of
broth constituents and test compounds. In the case
of the standard, a set of “8” sterilized test tube was
taken, to each of the test tubes, different solutions
were transferred aseptically as per the quantities
given below:
All the test tubes were kept for incubation for 48 h
at 37o
C, examined for growth of the test organism.
Test tube No. Test comp. (100 µg/ml) Inoculum Nutrient broth Final Conc. of test comp.
(µg/ml)
Solvent blank
(dimethylformamide)
1. 0.4 ml 0.1 ml 9.5 ml 4.0 -
2 0.6 ml 0.1 ml 9.3 ml 6.0 -
3 0.8 ml 0.1 ml 9.1 ml 8.0 -
4 1.0 ml 0.1 ml 8.9 ml 10.0 -
5 1.2 ml 0.1 ml 8.7 ml 12.0 -
6 - 0.1 ml 9.4 ml - 0.5 ml
7 - - 10 ml - -
8 1.1 ml - 8.9 ml 11.0 -

The MIC of the test compound was between the
lowest concentration inhibiting growth and the
highest concentration allowing growth. These two
concentrations for each synthesized were noted.
The exact MIC of each synthesized compound
was determined by repeating the experiment,
using a range of concentration between these
two concentrations. For example, the lowest
concentration inhibiting growth and highest
concentration allowing growth were 10 µg/ml
and 20 µg/ml, respectively, this means the MIC
of the test compound was between 10 µg/ml
and 20 µg/ml. The determination was repeated
with test compound concentration of 10 µg/ml,
11 µg/ml, 12 µg/ml, 20µg/ml to get the exact MIC
of the test compound. The final result of the MIC
determination of the synthesized compounds is
given in Table 1.
Antifungal screening of the synthesized
compounds
For antifungal screening, the following fungal
species were used includes
• Aspergillus niger (MTCC-281): It belongs
to the class deuteromycota. It reproduces by
means of a sexual spore formation known
as conidiospore, which is a unicellular or
multi-cellular spore that is not enclosed in a
sac.[22]
It is used in the fermentation industry
for the production of glucuronic acid as well
as citric acid. Many species of Aspergillus
are responsible for the human disease called
aspergillosis, and A. niger is a mold that is rarely
reported as a cause of pneumonia.[23]
The less
thermotolerant, ideal temperature for growth
is 30–34 °C, making germination difficult in
human body temperature of at least 37°C[24]
• Candida albicans (MTCC-227): It is pathogenic
yeast,whichbelongstothesameclassasA.niger.It
isresponsibleforthediseaseknownascandidiasis
that can affect skin, mucous membranes, and
nails.[25]
It produces chlamydospore, a thick-
walledsporeformedbyroundingandenlargement
within the hyphae segment. Morphologically, it is
yeast like with pseudohyphae
• Fusarium oxysporum (MTCC-284): It is a
frequent agent for a mycotic eye infection,
most commonly affecting the cornea. It is also
occasionally involved in a variety of infections,
including mycetoma, sinusitis, septic arthritis,
and nail infection[25]
• Clotrimazole (1-(o-chloro-α, α-diphenyl)
benzyl imidazole) was selected as standard
drug for antifungal study. It is a broad-spectrum
antifungal agent.[26]
Preparation of solution of standard drug
A stock solution of clotrimazole (1 mg/ml) was
prepared in DMF and further diluted as reported
for antibacterial studies.
Preparation of solution of the synthesized
compounds
The solutions were prepared in the same way as
mentioned under antibacterial screening.
Measurement of activity
MIC for standard drug, i.e., clotrimazole and for
synthesized compounds was determined using the
same procedure as described under antibacterial
screening. The result is shown in Table 2. Initial
Test tube No. Norfloxacin (100 µg/ml) Inoculum NB Final concentration of norfloxacin (µg/ml)
1. 0.05 ml 0.1 ml 9.85 ml 0.5
2. 0.1 ml 0.1 ml 9.8 ml 1.0
3. 0.2 ml 0.1 ml 9.7 ml 2.0
4. 0.4 ml 0.1 ml 9.5 ml 4.0
5. 0.6 ml 0.1 ml 9.3 ml 6.0
6. 0.8 ml 0.1 ml 9.1 ml 8.0
7. 1.0 ml 0.1 ml 8.9 ml 10.0
8. 1.2 ml 0.1 ml 8.7 ml 12.0

antimicrobial activity data for the quinazolinone
analogs are reported in Tables 1 and 2, along with
the literature data on clotrimazole.
RESULTS AND DISCUSSION
Spectral analysis
The structures of the synthesized compounds
(QNM-1 to QNM-15) were characterized by IR,
13C NMR spectra, and mass spectroscopy. The
IR spectra of the synthesized compounds showed
characteristic absorption band between 1680 and
1700 cm−1
due to C=O str (quinazolinone ring);
between 1600 and 1650 cm−1
due to C=C str.
(vinyl group); between 1520 and 1560 cm−1
due
to C=N str. (1,3,4-thiadiazole and quinazolinone
ring); between 1210 and 1250 due to C-N str of
quinazolinone ring; between 550 and 780 cm−1
due to C-S str. (1,3,4-thiadiazole ring); 1090 cm−1
due toAr-Cl str. and between 400 and 500 cm−1
due
to aryl C-Cl in chloro containing compounds and
3163.3 C-H str. (Aromatic ring).
In 13C-NMR spectra of the synthesized compounds
C-2andC-4ofquinazolinonewereobservedbetween
160–165 and 167–168 (δ, ppm), respectively, C-11
and (C-5, C-6, C-7, C-8, C-9, C-10, C-12, C-13,
C-14 and C18, C16, C15 and C17, and C16) of
quinazolinone were observed between 112–115
and 122.1–147.8 (δ, ppm) respectively. Methyl
carbons were observed at 21.3 ppm. In addition,
peaks at δ 77.0 ppm for CDCl3 (solvent) and at
δ 39.0 ppm for dimethyl sulfoxide -d6 (solvent)
were also observed in respective cases. Elemental
analysis of all synthesized compounds was within
the ±0.4% of the theoretical values. Generation of
dense sooty flame and formation of oily layer after
nitration of the compounds confirmed the presence
of aromatic ring in all the synthesized compounds.
In the FAB mass spectra, two prominent peaks
were observed. TLC has been executed for the
monitored of reaction and purity of the synthesized
compounds using silica gel G in various solvent
systems such as hexane/ethanol (95%)/chloroform/
benzene, and iodine chamber has been used for the
visualization and in some cases UV chamber used.
All these characterization parameters showed that
the structure of the synthesized compounds was
near to expected.
QNM-1: (E)-3-(5-((phenylamino)methyl)-1,3,4-
thiadiazol-2-yl)-2-styrylquinazolin-4(3H)-one
Molecularformula:C25
H19
N5
OS;Molecularweight:
437.52; TLC (Rf value):0.45; element analysis
Table 2: Antifungal activity of the synthesized compounds
Codes Ar R1
R2
Antifungal activity minimum inhibitory concentration in µg/ml
Aspergillus niger
(MTCC-281)
C. albicans
(MTCC-227)
Fusarium oxysporum
(MTCC-284)
QNM-1 -C6
H5
-C6
H5
H 12.30±0.24 10.28±1.08 10.58±0.18
QNM-2 -C6
H5
-C6
H5
Cl (o) H 14.48±0.64 13.88±0.34 13.20±0.44
QNM-3 -C6
H5
-C6
H5
Cl (m) H 15.28±1.64 14.84±1.88 14.48±1.46
QNM-4 -C6
H5
-C6
H5
F (m) H 12.66±0.88 10.44±0.85 12.64±0.32
QNM-5 -C6
H5
-C6
H5
NO2
(p) H 11.42±0.22 7.23±1.02 10.13±0.20
QNM-6 -C6
H5
-C6
H5
Br(o) H 16.24±0.26 12.38±0.66 13.46±0.60
QNM-7 -C6
H5
Br -C6
H5
Br (p) H 11.46±0.58 7.04 ±0.82 10.41±0.40
QNM-8 -C6
H5
Br -C6
H5
F (p) H 13.56±0.66 7.58±0.20 12.34±0.57
QNM-9 -C6
H5
Br -C6
H5
NO2
(p) H 11.90±0.76 6.88±1.20 10.68±0.54
QNM-10 -C6
H5
F -C6
H5
F (o) H 14.84±0.70 13.68 ±0.66 14.64 ±0.22
QNM-11 -C6
H5
F -C6
H5
NO2
(p) H 11.40±0.21 7.85±0.52 10.60±0.98
QNM-12 -C6
H5
CH3
-C6
H5
Cl (p) H 11.64±0.30 6.75±0.50 9.95±0.82
QNM-13 -C6
H5
CH3
-C6
H5
F (p) H 13.44±0.36 6.60±1.10 11.26±0.46
QNM-14 -C6
H5
CH3
-C6
H5
NO2
(p) H 11.40±0.26 7.30±0.62 10.26±0.76
QNM-15 -C6
H5
CH3
-C6
H5
Br (p) H 11.68±0.36 6.44 ±0.58 10.20±0.24
Clotrimazole 11.56±0.32 6.40±0.26 9.88±0.71

found (Calculated): Nitrogen (%) 16.01 (15.98);
sulfur (%) 7.33 (7.31); oxygen (%) 3.66 (3.64). IR
(cm−1
): 3020 (C-H str.); 760 (C-H def.); 1700 (C=O
str.); 1174 (-C6
H5
); 1516 (C=C str.) 2856 (C-H str.);
3120 (C-H str.); 1461 (C-H str.); 1580 (C-C str.);
1614 (C=C str.); 1326 (C-N str.) 1555 (C=N str.);
760 (C-S str.) 13C NMR (ppm): 113.3 (C11 due
to styryl group attached to 4-quinazolinone ring);
126.7 (C8 due to 4-quinazolinone ring); 128.5
(C14
and C18
due to phenyl substituted styryl group
attached to 4-quinazolinone ring); 145.5 (C9, due
to 4-quinazolinone ring and phenyl ring attached
to 1,3,4 thiadiazole ring); 127.9 (C16
due to phenyl
substitutedstyrylgroupattachedto4-quinazolinone
ring); 127.3 (C6 due to 4-quinazolinone ring);
128.6 (C15 and C17, due to phenyl substituted
styryl group attached to 4-quinazolinone ring
and phenyl ring attached to 1,3,4-thiadiazole
ring); 129.6, due to phenyl ring attached to 1,3,4
thiadiazole ring; 126.6, C5 due to 4-quinazolinone
ring; 133.4, C7 due to 4-quinazolinone ring; 135.2,
C13 due to phenyl substituted styryl group attached
to 4-quinazolinone ring; 138.1, C12 due to styryl
group attached to 4-quinazolinone ring; 147.4, C14
due to phenyl ring attached to 1,3,4 thiadiazole
ring; 120.8, C10 due to 4-quinazolinone ring;
158.9, C2 due to 4-quinazolinone ring; 160.6, C4
due to 4-quinazolinone ring; and 51.3a, due to
CH2–NH attached to 1,3,4 thiadiazole ring. FAB
Mass (m/z): 437.11.
QNM-2: (E)-3-(5-(((4-chlorophenyl)amino)
methyl)-1,3,4-thiadiazol-2-yl)-2-styryl
quinazolin-4(3H)-one
Molecular formula:C25
H18
ClN5
OS; Molecular
weight: 471.96; TLC (Rf value): 0.65; elemental
analysis found (Calculated): Nitrogen (%) 14.82
(14.84); sulfur (%) 6.72 (6.79); oxygen (%) 3.37
(3.39); IR (cm−1
): 3020 C-H str.; 760 C-H def.; 1700
C=O str.; 1174 -C6H5; 1516 C=C str.; 2856 C-H
str.; 3120 C-H str.; 1461 C-H str.; 1580 C-C str.;
1614 C=C str.; 1326 C-N str.; 1555 C=N str.; 760
C-S str.; 1538 C-Cl str.; 13C NMR (ppm):113.3,
C11 due to styryl group attached to 4-quinazolinone
C14 and C18 due to phenyl substituted styryl group
attached to 4-quinazolinone ring; 145.5, C9 due to
4-quinazolinone ring and phenyl ring attached to
1,3,4 thiadiazole ring; 127.9, C16 due to phenyl
ring; 127.3, C6 due to 4-quinazolinone ring 128.6,
C15 and C17 due to phenyl substituted styryl
group attached to 4-quinazolinone ring and phenyl
ring attached to 1,3,4-thiadiazole ring; 129.6, due
to phenyl ring attached to 1,3,4 thiadiazole ring;
126.6, C5 due to 4-quinazolinone ring; 133.4,
C7 due to 4-quinazolinone ring; 135.2 C13 due
to phenyl substituted styryl group attached to
4-quinazolinone ring; 138.1, C12 due to styryl
group attached to 4-quinazolinone ring; 147.4, due
C2 due to 4-quinazolinone ring; 160.6, C4 due to
4-quinazolinone ring; and 51.3 a, due to CH2–NH
attached to 1,3,4 thiadiazole ring; FAB Mass (m/z):
472.00.
QNM-3: (E)-3-(5-(((4-chlorophenyl)amino)
Molecular formula: C25
H18
ClN5
OS; molecular
analysis: Found (Calculated): Nitrogen (%) 14.82
(14.84); sulfur (%) 6.72 (6.79); oxygen (%) 3.37
(3.39); IR (cm−1
): 3020 C-H str.; 760 C-H def; 1700
C=O str.; 1174 -C6H5; 1516 C=C str.; 2856 C-H
str.; 3120 C-H str.; 1461 C-H str.; 1580 C-C str.;
C-S str.; 1542 C-Cl str.; 13C NMR (ppm): 113.3,
C11duetostyrylgroupattachedto4-quinazolinone

C7 due to 4-quinazolinone ring; 135.2, C13 due
to 4-quinazolinone ring; and 51.3a, due to CH2
–
NH attached to 1,3,4 thiadiazole ring; FAB Mass
(m/z): 472.
QNM-4: (E)-3-(5-(((2-fluorophenyl)amino)
H18
FN5
OS;molecularweight:
455.51; TLC (Rf value): 0.68; elemental analysis:
Found (Calculated): Nitrogen (%) 15.35 (15.37);
sulfur (%) 7.02 (7.04); Oxygen (%) 3.45 (3.51); IR
(cm−1
): 3261 C-H str.; 886 C-H def (oop);1700 C=O
str.; 1174 -C6H5; 1540 N=0 str.; 1320 N-O str.; 1593
C=C str.; 2856 C-H str.; 3057 C-H str.; 1382 C-H
def; 1442 C-C str.; 1620 C=C str.; 1274 C-N str.;
740 C-S str.; 650 C-F str.; 13C NMR (ppm): 113.5,
substituted styryl group attached to 4-quinazolinone
group attached to 4-quinazolinone ring; 155.4,
phenyl ring attached to 1,3,4 thiadiazole ring;
4-quinazolinone ring; and 51.1 a, due to CH2
–NH
attached to 1,3,4 thiadiazole ring; FAB mass (m/z):
455.31.
QNM-5: (E)-3-(5-(((4-nitrophenyl)amino)
H18
N6
O3
S; molecular
(17.42); sulfur (%) 6.60 (6.65); oxygen (%) 9.90
(9.95); IR (cm−1
): 3261 C-H str.; 831 C-H def (oop);
1700 C=O str.;1174 -C6H5; 1540 N=0 str.; 1320
N-O str.; 1593 C=C str.; 856 C-H str.; 3057 C-H str.;
1382 C-H def; 1442 C-C str.; 1620 C=C str.; 1274
C-N str.; 740 C-S str.; 13C NMR (ppm): 113.5, C11
due to styryl group attached to 4-quinazolinone
4-quinazolinone ring; and 51.1a, due to CH2
–NH
482.
QNM-6: (E)-3-(5-(((4-bromophenyl)amino)
H18
BrN5
OS; molecular
(13.56); sulfur (%) 6.18 (6.21); oxygen (%) 3.09
(3.10); IR (cm−1
): 3211 C-H str.; 774 C-H def (oop);
1701 C=O str.; 1596 C=C str.; 2896 C-H str.; 3060
C-H str.; 1447 C-H def; 1470 C-C str.; 1637 C=C

str.; 1316 C-N str.; 1530 C=N str.; 719 C-S str.;
570 C-Br str.; 13C NMR (ppm): 113.2, C11 due
to styryl group attached to 4-quinazolinone ring;
and C18 due to phenyl substituted styryl group
–
NH attached to 1,3,4 thiadiazole ring; FAB mass
(m/z): 516.13.
quinazolin -4(3H)-one
H18
N6
O3
S; molecular weight:
sulfur (%) 6.60 (6.65); oxygen (%): 9.90 (9.95);
IR (cm-1): 3125 (C-H str.); 808 (C-H def (oop);
1700 (C=O str.; 1590 C=C str.; 2945 C-H str.; 3050
C-H str.; 1450 C-H def.; 1570 C-C str.; 1630 C=C
str.; 1348 C-N str.; 1560 C=N str.; 575 C-S str.;
126.2 C8 due to 4-quinazolinone ring: 128.5, C14
attached to 4-quinazolinone ring and phenyl ring
attached to 1,3,4-thiadiazole ring; 116.3, phenyl ring
attached to 1,3,4 thiadiazole ring; 126.3, C5 due to
4-quinazolinonering;133.7,C7dueto4-quinazolinone
ring; 135.2, C13 due to phenyl substituted styryl
due to styryl group attached to 4-quinazolinone
ring; 144.9, phenyl ring attached to 1,3,4 thiadiazole
ring; 120.5, C10 due to 4-quinazolinone ring 158.2,
–
(m/z): 482.51.
H18
N6
O3
S; molecular weight:
482.51; TLC (Rf value): 0.67; elemental analysis
found (Calculated): Nitrogen (%) 17.38 (17.42);
sulfur (%) 6.60 (6.65); oxygen (%) 9.90 (9.95); IR
(cm−1
): 3074 C-H str.; 718 C-H def (oop); 1734 C=O
str.; 1580 N=O str.; 1350 N-O str.; 1597.1 C=C str.;
2944 C-H str.; 3020 C-H str.; 1380 C-H def.; 1456
C-C str.; 1634 C=C str.; 1239 C-N str.; 658 C-S str.;
126.4 C8 due to 4-quinazolinone ring; 128.4 C14
4-quinazolinoneringandphenylringattachedto1,3,4
thiadiazole ring; 133.5, C16 due to phenyl substituted
styryl group attached to 4-quinazolinone ring; 129.1,
C6 due to 4-quinazolinone ring; 136.3, C15 and C17,
C due to phenyl substituted styryl group attached
to 1,3,4-thiadiazole ring; 129.6, due to phenyl ring
group attached to 4-quinazolinone ring;138.2, C12
due to styryl group attached to 4-quinazolinone ring;
155.4, due to phenyl ring attached to 1,3,4 thiadiazole

–
(m/z): 482.51.
QNM-9: (E)-2-(4-bromostyryl)-3-(5-(((4-
nitrophenyl)amino)methyl)-1,3,4-thiadiazol-2-
yl) quinazolin-4(3H)-one
H17
BrN6
O3
S; molecular
(14.97); sulfur (%) 5.68 (5.71); oxygen (%) 8.45
(8.55); IR (KBr, cm-1): 3159 C-H str.; 761 C-H def
(oop); 1701 C=O str.; 1562 C=C str.; 2907 C-H str.;
3010C-Hstr.;1375C-Hdef;1439C-Cstr.;1693C=C
str.; 1274 C-N str.; 754 C-S str.; 520 C-Br str.; 1540
N=0 str.; 1320 N-O str.; 13C NMR (ppm): 113.3,
C11 due to styryl group attached to 4 quinazolinone
attached to 4 quinazolinone ring; 113.4, C9 due to
ring;120.2, C10 due to 4-quinazolinone ring;158.3,
C2 due to 4-quinazolinone ring; 160.6 C4 due to
4-quinazolinone ring; and 51.5 a, due to CH2–NH
561.41.
QNM-10: (E)-3-(5-(((2-fluorophenyl)amino)
methyl)-1,3,4-thiadiazol-2-yl)-2-(4-fluoro
styryl)quinazolin-4(3H)-one
H17
F2
N5
OS; molecular
weight: 473.50; TLC (Rf value):0.62; elemental
(14.79); sulfur (%) 6.74 (6.77); oxygen (%) 3.32
(3.38); IR (KBr, cm-1): 3157 C-H str.; 819 C-H
def (oop); 1703 C=O str.; 1080 C-O-C str.; 1559
C=C str.; 2909 C-H str.; 3050 C-H str.; 1417
C-H def.; 1450 C-C str.; 1609 C=C str.; 1252
C-N str.; 1519 C=N str.; 615 C-S str.; 650 C F
str.; 13C NMR (ppm): 113.1, C11 due to styryl
C8 due to 4-quinazolinone ring; 128.3, C14
attached to 4 quinazolinone ring; 113.3, C9 due to
151.7, C15 and C17 due to phenyl substituted
styryl group attached to 4-quinazolinone ring and
phenyl ring attached to 1,3,4-thiadiazole ring;
to 4-quinazolinone ring; and 160.8, C4 due to
4-quinazolinone ring; 51.5 a, due to CH2
–NH
attached to 1,3,4 thiadiazole ring: FAB mass (m/z):
473.16.
QNM-11: (E)-2-(4-fluorostyryl)-3-(5-(((4-
nitrophenyl)amino)methyl)-1,3,4-thiadiazol-2-
yl)quinazolin-4(3H)-one
H17
FN6
O3
S;molecularweight:
sulfur (%) 6.39 (6.41); oxygen (%) 9.57 (9.59); IR
(KBr, cm−1
): 3160 C-H str; 760 C-H def (oop); 1693
C=O str.; 1590 C=C str.; 2902 C-H str.; 3020 C-H str.;
1373 C-H def.; 1437 C-C str.; 1580 N=0 str.; 1370
N-O str.; 1610 C=C str.; 1316 C-N str.; 1568 C=N str.;

126.1, C5 due to 4-quinazolinone ring; 133.7
120.8, C10 due to 4-quinazolinone ring; 158.2
C2, due to 4-quinazolinone ring; 160.3, C4 due
to 4-quinazolinone ring; and 51.3 a, due to CH2
–
(m/z): 500.50.
QNM-12: (E)-3-(5-(((4-chlorophenyl)
amino)methyl)-1,3,4-thiadiazol-2-yl)-2-(4-
methylstyryl) quinazolin-4(3H)-one
H20
ClN5
OS; molecular
(14.41); sulfur (%) 6.56 (6.60);Oxygen (%) 3.25
(3.29); IR (KBr, cm−1
): 3117.3 C-H str.; 752.8 C-H
def (oop); 1689.5 C=O str.; 1594 C=C str.; 2917 C-H
str.; 3020 C-H str.; 1448.3 C-H def.; 1240 C-C str.;
C-S str.; 464.4 C-Cl str.; 13C NMR (ppm): 113.4,
attached to 4-quinazolinone ring; 114.4, C9, due to
4-quinazolinoneringandphenylringattachedto1,3,4
thiadiazole ring; 137.6, C16 due to phenyl substituted
styryl group attached to 4-quinazolinone ring; 127.1,
C6 due to 4-quinazolinone ring; 128.9, C15 and
C17 due to phenyl substituted styryl group attached
to 1,3,4-thiadiazole ring; 129.4due to phenyl ring
due to styryl group attached to 4-quinazolinone ring;
147.4, due to phenyl ring attached to 1,3,4 thiadiazole
4-quinazolinone ring; 51.1a, due to CH2
–NH attached
to 1,3,4 thiadiazole ring; 15.4 CH3; and phenyl
ring; FAB Mass (m/z): 486.13.
QNM-13: (E)-3-(5-(((4-fluorophenyl)
amino)methyl)-1,3,4-thiadiazol-2-yl)-2-(4-
methylstyryl) quinazolin-4(3H)-one
H20
FN5
OS; molecular
analysis: Found (Calculated): Nitrogen (%) 14.95
(14.92); sulfur (%) 6.82 (6.83); oxygen (%) 3.38
(3.41); IR (KBr, cm−1
): 3163.3 C-H str.; 822 C-H def
(oop); 1691.4 C=O str.; 1568.1 C=C str.; 2911 C-H
str.; 3032.5 C-H str.; 1374.6 C-H def. 1438.2 C-C
str.; 1600 C=C str.; 1313.7 C-N str.; 1520 C=N str.;
due to 4-quinazolinone ring; 51.3 a, due to CH2–
NH attached to 1,3,4 thiadiazole ring; and 15.4,
CH3
phenyl substituted styryl group attached to
4-quinazolinone ring; FAB mass (m/z): 469.23

IJPBA_11(2)_20_20200819_V1.pdf

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