Drug design is the inventive process of finding new medications based on the knowledge of the biological target.
In the most basic sense, drug design involves design of small molecules that are complementary in shape and charge to the bio-molecular target to which they interact and therefore will bind to it.
Drug design frequently but not necessarily relies on computer modeling techniques. This type of modeling is often referred to as computer-aided drug design.
Types;-
Random screening
Trial and error method
Ethnopharmacology approach
Serendipity method
Classical pharmacology
Chemical structure based drug discovery
Pharmacology Made Simple For Nursing Studentsrachelvijaya
Pharmacology is one of the tough subjects for Nursing Students and my intention is to make it attractive and easy to learn for the students.
"Nothing in Life is to be feared, it is only to be understood. Now is the time to understand more, so that we may fear less."
- Marie Curie
Only a privileged few win the Nobel Prize in their lifetime. Even fewer do so in the scientific category without a medical or a doctorate. Tu Youyou, a Chinese chemist and Malariologist did just that. She won the Nobel in Physiology or Medicine in 2015 for discovering an anti-malaria drug called artemisinin.
Drug design is the inventive process of finding new medications based on the knowledge of the biological target.
In the most basic sense, drug design involves design of small molecules that are complementary in shape and charge to the bio-molecular target to which they interact and therefore will bind to it.
Drug design frequently but not necessarily relies on computer modeling techniques. This type of modeling is often referred to as computer-aided drug design.
Types;-
Random screening
Trial and error method
Ethnopharmacology approach
Serendipity method
Classical pharmacology
Chemical structure based drug discovery
Pharmacology Made Simple For Nursing Studentsrachelvijaya
Pharmacology is one of the tough subjects for Nursing Students and my intention is to make it attractive and easy to learn for the students.
"Nothing in Life is to be feared, it is only to be understood. Now is the time to understand more, so that we may fear less."
- Marie Curie
Only a privileged few win the Nobel Prize in their lifetime. Even fewer do so in the scientific category without a medical or a doctorate. Tu Youyou, a Chinese chemist and Malariologist did just that. She won the Nobel in Physiology or Medicine in 2015 for discovering an anti-malaria drug called artemisinin.
Antimalarial metabolization: what have we learnt so far?Premier Publishers
Considering malaria is a highly devastating disease of mankind, total eradication of malaria seems to be an uphill task, the only relief from this disease is achieved by usage of antimalarial drugs. Since malaria is associated with humans from time immemorial, usage of traditional substances to most presently effective antimalarial have been recorded to cure this disease. With the advent of modern biological techniques aided the understanding of the biochemical pathways of antimalarial metabolism thereby helping in designing successful usage of many antimalarials. Nevertheless, improper usages of certain drugs have led to the origin and spread of drug resistant malaria parasites (chloroquine resistant Plasmodium falciparum). Also, the genetic basis of antimalarial metabolism in humans is now well understood and frequent mutations in genes of malarial parasites are well associated with drug resistance. The entire scenario of antimalarial usage in the field have become complicated, partly due to poor understanding between antimalarial metabolism in humans and drug fighting mechanism in parasites, by which resistance to even combined therapy (e.g. Artemisinin Combination Therapy) have started emerging. Vital basic understanding from human and parasite population genetics (involving antimalarial both metabolizing genes in human and resistant genes in parasite) could be an ideal starting point to malaria control.
Drug discovery is the process through which potential new medicines are identified.
It involves a wide range of scientific disciplines, including biology, chemistry and pharmacology.
Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases.
Natural products also have challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization.
The Use Of Antibiotic In Food Producing Animals ,Dina m.
what is antibiotic, Why are antibiotics used in food-producing animals?, Which antibiotics used in food-producing animals are related to antibiotics used in humans?
1.1 Pharmacology- An Introduction
The word pharmacology is derived from two Greek words, pharmacon meaning a drug, and logos meaning an opinion or reason. It can be defined as
“The science which deals with the history, source, physical properties, chemical properties, compounding, biochemical effects, physiological effects, mechanism of action, absorption, distribution, biotransformation, excretion, therapeutic and other uses of drugs, is called pharmacology.”
“The study of a substance that interacts with the living system through chemical processes especially by binding to regulatory molecules and activates or inhibits normal body processes”
“The science of substances used to prevent, diagnose and treat disease.”
Drug:
The word drug comes from Drogue meaning a dry herb. A drug can be defined as:
“A substance, material or product used for the purpose of diagnosis, prevention and relief of symptoms or cure of disease.”
WHO defines drug as:
“A substance, material or product used or intended to be used to modify or explore the physiological processes or pathological states for the benefit of the recipient.”
General Features of a Drug:
• Variability in molecular size
• Variability in shape
• Variability in chemical nature
• Variability in lipid/water partition coefficient
• Variability in degree of ionization
• Physical Properties
• Variability in molecular size
Smaller sized molecules are easily absorbed than larger molecules. Normally the molecular weight is between 100-1000 but may be higher or lower. Streptokinase is an example of large molecular weight drug while lithium or nitric oxides are of small molecular weight.
• Variability in shape
Antimalarial metabolization: what have we learnt so far?Premier Publishers
Considering malaria is a highly devastating disease of mankind, total eradication of malaria seems to be an uphill task, the only relief from this disease is achieved by usage of antimalarial drugs. Since malaria is associated with humans from time immemorial, usage of traditional substances to most presently effective antimalarial have been recorded to cure this disease. With the advent of modern biological techniques aided the understanding of the biochemical pathways of antimalarial metabolism thereby helping in designing successful usage of many antimalarials. Nevertheless, improper usages of certain drugs have led to the origin and spread of drug resistant malaria parasites (chloroquine resistant Plasmodium falciparum). Also, the genetic basis of antimalarial metabolism in humans is now well understood and frequent mutations in genes of malarial parasites are well associated with drug resistance. The entire scenario of antimalarial usage in the field have become complicated, partly due to poor understanding between antimalarial metabolism in humans and drug fighting mechanism in parasites, by which resistance to even combined therapy (e.g. Artemisinin Combination Therapy) have started emerging. Vital basic understanding from human and parasite population genetics (involving antimalarial both metabolizing genes in human and resistant genes in parasite) could be an ideal starting point to malaria control.
Drug discovery is the process through which potential new medicines are identified.
It involves a wide range of scientific disciplines, including biology, chemistry and pharmacology.
Natural products and their structural analogues have historically made a major contribution to pharmacotherapy, especially for cancer and infectious diseases.
Natural products also have challenges for drug discovery, such as technical barriers to screening, isolation, characterization and optimization.
The Use Of Antibiotic In Food Producing Animals ,Dina m.
what is antibiotic, Why are antibiotics used in food-producing animals?, Which antibiotics used in food-producing animals are related to antibiotics used in humans?
1.1 Pharmacology- An Introduction
The word pharmacology is derived from two Greek words, pharmacon meaning a drug, and logos meaning an opinion or reason. It can be defined as
“The science which deals with the history, source, physical properties, chemical properties, compounding, biochemical effects, physiological effects, mechanism of action, absorption, distribution, biotransformation, excretion, therapeutic and other uses of drugs, is called pharmacology.”
“The study of a substance that interacts with the living system through chemical processes especially by binding to regulatory molecules and activates or inhibits normal body processes”
“The science of substances used to prevent, diagnose and treat disease.”
Drug:
The word drug comes from Drogue meaning a dry herb. A drug can be defined as:
“A substance, material or product used for the purpose of diagnosis, prevention and relief of symptoms or cure of disease.”
WHO defines drug as:
“A substance, material or product used or intended to be used to modify or explore the physiological processes or pathological states for the benefit of the recipient.”
General Features of a Drug:
• Variability in molecular size
• Variability in shape
• Variability in chemical nature
• Variability in lipid/water partition coefficient
• Variability in degree of ionization
• Physical Properties
• Variability in molecular size
Smaller sized molecules are easily absorbed than larger molecules. Normally the molecular weight is between 100-1000 but may be higher or lower. Streptokinase is an example of large molecular weight drug while lithium or nitric oxides are of small molecular weight.
• Variability in shape
Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
The Valsalva maneuver exerts pressure to expel faeces through a voluntary contraction of the abdominal muscles while maintaining forced expiration against a closed airway. Patients with cardiovascular disease, glaucoma, increased intracranial pressure, or a new surgical wound are at greater risk for cardiac dysrhythmias and elevated blood pressure with the Valsalva maneuver and need to avoid straining to pass the stool.
Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
Fecal impaction results from unrelieved constipation. It is a collection of hardened feces wedged in the rectum that a person cannot expel. In cases of severe impaction the mass extends up into the sigmoid colon.
DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
PREPARATION AND GIVING OF LAXATIVESACCORDING TO POTTER AND PERRY,
An enema is the instillation of a solution into the rectum and sig
Navigating Challenges: Mental Health, Legislation, and the Prison System in B...Guillermo Rivera
This conference will delve into the intricate intersections between mental health, legal frameworks, and the prison system in Bolivia. It aims to provide a comprehensive overview of the current challenges faced by mental health professionals working within the legislative and correctional landscapes. Topics of discussion will include the prevalence and impact of mental health issues among the incarcerated population, the effectiveness of existing mental health policies and legislation, and potential reforms to enhance the mental health support system within prisons.
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
Global launch of the Healthy Ageing and Prevention Index 2nd wave – alongside...ILC- UK
The Healthy Ageing and Prevention Index is an online tool created by ILC that ranks countries on six metrics including, life span, health span, work span, income, environmental performance, and happiness. The Index helps us understand how well countries have adapted to longevity and inform decision makers on what must be done to maximise the economic benefits that comes with living well for longer.
Alongside the 77th World Health Assembly in Geneva on 28 May 2024, we launched the second version of our Index, allowing us to track progress and give new insights into what needs to be done to keep populations healthier for longer.
The speakers included:
Professor Orazio Schillaci, Minister of Health, Italy
Dr Hans Groth, Chairman of the Board, World Demographic & Ageing Forum
Professor Ilona Kickbusch, Founder and Chair, Global Health Centre, Geneva Graduate Institute and co-chair, World Health Summit Council
Dr Natasha Azzopardi Muscat, Director, Country Health Policies and Systems Division, World Health Organisation EURO
Dr Marta Lomazzi, Executive Manager, World Federation of Public Health Associations
Dr Shyam Bishen, Head, Centre for Health and Healthcare and Member of the Executive Committee, World Economic Forum
Dr Karin Tegmark Wisell, Director General, Public Health Agency of Sweden
Telehealth Psychology Building Trust with Clients.pptxThe Harvest Clinic
Telehealth psychology is a digital approach that offers psychological services and mental health care to clients remotely, using technologies like video conferencing, phone calls, text messaging, and mobile apps for communication.
Struggling with intense fears that disrupt your life? At Renew Life Hypnosis, we offer specialized hypnosis to overcome fear. Phobias are exaggerated fears, often stemming from past traumas or learned behaviors. Hypnotherapy addresses these deep-seated fears by accessing the subconscious mind, helping you change your reactions to phobic triggers. Our expert therapists guide you into a state of deep relaxation, allowing you to transform your responses and reduce anxiety. Experience increased confidence and freedom from phobias with our personalized approach. Ready to live a fear-free life? Visit us at Renew Life Hypnosis..
CHAPTER 1 SEMESTER V - ROLE OF PEADIATRIC NURSE.pdfSachin Sharma
Pediatric nurses play a vital role in the health and well-being of children. Their responsibilities are wide-ranging, and their objectives can be categorized into several key areas:
1. Direct Patient Care:
Objective: Provide comprehensive and compassionate care to infants, children, and adolescents in various healthcare settings (hospitals, clinics, etc.).
This includes tasks like:
Monitoring vital signs and physical condition.
Administering medications and treatments.
Performing procedures as directed by doctors.
Assisting with daily living activities (bathing, feeding).
Providing emotional support and pain management.
2. Health Promotion and Education:
Objective: Promote healthy behaviors and educate children, families, and communities about preventive healthcare.
This includes tasks like:
Administering vaccinations.
Providing education on nutrition, hygiene, and development.
Offering breastfeeding and childbirth support.
Counseling families on safety and injury prevention.
3. Collaboration and Advocacy:
Objective: Collaborate effectively with doctors, social workers, therapists, and other healthcare professionals to ensure coordinated care for children.
Objective: Advocate for the rights and best interests of their patients, especially when children cannot speak for themselves.
This includes tasks like:
Communicating effectively with healthcare teams.
Identifying and addressing potential risks to child welfare.
Educating families about their child's condition and treatment options.
4. Professional Development and Research:
Objective: Stay up-to-date on the latest advancements in pediatric healthcare through continuing education and research.
Objective: Contribute to improving the quality of care for children by participating in research initiatives.
This includes tasks like:
Attending workshops and conferences on pediatric nursing.
Participating in clinical trials related to child health.
Implementing evidence-based practices into their daily routines.
By fulfilling these objectives, pediatric nurses play a crucial role in ensuring the optimal health and well-being of children throughout all stages of their development.
One of the most developed cities of India, the city of Chennai is the capital of Tamilnadu and many people from different parts of India come here to earn their bread and butter. Being a metropolitan, the city is filled with towering building and beaches but the sad part as with almost every Indian city
How many patients does case series should have In comparison to case reports.pdfpubrica101
Pubrica’s team of researchers and writers create scientific and medical research articles, which may be important resources for authors and practitioners. Pubrica medical writers assist you in creating and revising the introduction by alerting the reader to gaps in the chosen study subject. Our professionals understand the order in which the hypothesis topic is followed by the broad subject, the issue, and the backdrop.
https://pubrica.com/academy/case-study-or-series/how-many-patients-does-case-series-should-have-in-comparison-to-case-reports/
We understand the unique challenges pickleball players face and are committed to helping you stay healthy and active. In this presentation, we’ll explore the three most common pickleball injuries and provide strategies for prevention and treatment.
QA Paediatric dentistry department, Hospital Melaka 2020Azreen Aj
QA study - To improve the 6th monthly recall rate post-comprehensive dental treatment under general anaesthesia in paediatric dentistry department, Hospital Melaka
5. The 2015 Nobel Prize in Physiology
or Medicine was awarded to
Professor Youyou Tu for her key
contributions to the discovery of
artemisinin.
Tu Youyou turned to Chinese medical texts from the
Zhou, Qing, and Han Dynasties to find a traditional
cure for malaria, ultimately extracting a compound –
artemisinin – that has saved millions of lives. When she
isolated the ingredient she believed would work, she
volunteered to be the first human subject.
6. Do you know about drug development life cycle?
And, what is drug development process timeline?
For a new drug to get approved in the US, it takes ~12-15
years! That’s roughly 1/3rd of our entire professional
career. Next, how much investment do you think is
required for drug discovery design and development to
bring a new drug to market? A colossal sum of money,
~$1 billion, that’s equivalent to employing 665+
employees at the annual salary of $100k for 15 years.
7. The complexity in drug development has
increased manifolds over the past 40 years,
requiring preclinical phase of drug
development, investigational new drug (IND)
application, and complete clinical testing
before marketing approval from the FDA.
Generally, new drug applications (NDAs) or
biologics license applications (BLA)
are reviewed comprehensively before
approval, and then drug performance is
resubmitted to regulatory agencies for post-
marketing studies.
The overarching goal is to bring more
efficient and safer treatments to the patients
as quickly as possible after a thorough
medical evaluation.
8. Drug discovery research is how new medications are discovered. Historically, drug discovery, design, and development
mostly started with identifying active ingredients from traditional medicines or purely by chance. Later, classical
pharmacology was used to investigate chemical libraries including small molecules, natural products, or plant extracts,
and find those with therapeutic effects.
9. Target Identification And Validation
During the early stages of drug discovery
for a certain disease, the underlying
molecular mechanisms behind the disease are
studied. These studies include identifying
the cellular and genetic factors involved
in the disease, followed by the
identification of potential targets. In
order to ensure that the biological target
is involved in the disease, in
vitro (isolated cells) and in vivo (animal
models) tests are performed. This is also
known as the target validation stage.
Modern target validation often involves a
combination of in vitro, in vivo, and in
silico (performed with a computer)
studies. The results of the target
validation stage can assist in lead
compound identification.
10. Lead compounds are chemical compounds that
show desired biological or pharmacological
activity and may initiate the development of a
new clinically relevant compound. Lead
compounds are typically used as starting points
in drug design to give new drug entities. Drug
design strategies can be used to improve the
compound’s pharmacodynamic and
pharmacokinetic properties.
Possible sources of lead compounds and novel
drugs include:
1.Natural products
2.Chemical libraries
3.Computational medicinal chemistry
What are Lead Compounds ?
16. Lead Optimization
In the lead optimization (LO) process, the lead compounds
discovered are synthesized and modified to improve potency
and reduce side effects. Lead optimization conducts
experimental testing using animal efficacy models and ADMET
tools, designing the drug candidate.
The drug discovery process gets narrowed
when one lead compound is found for a
drug candidate, and the process of drug
development starts
17.
18. Formulation Optimization & Improving Bioavailability
Formulation optimization is ongoing throughout pre-clinical and clinical stages. It ensures drugs are delivered to the
proper place at the right time and in the right concentration. Optimization may include overcoming solubility
26. Malaria
Malaria is an infectious disease known since ancient times. The name comes
from the words ‘mala aria‘ meaning ‘bad air’. Malaria was associated with regions
that are badly drained, swamps, and marshes. The disease is caused by a
protozoal parasite (genus plasmodium), which is carried by female mosquitos
(genus Anopheles). Species of genus plasmodium associated with malaria
include vivax, malariae, falciparum, and ovale. Plasmodium falciparum poses the greatest
danger to humans and it is known to affect up to 65% of an infected person’s
erythrocytes. Transmission between infected mosquitos and humans occur through
27. Controlling & Treating Malaria
Natural compounds from the bark of the cinchona tree,
most notably quinine was observed to exhibit
antimalarial activity. Until the development of
synthetic derivatives (ie. 4-aminoquinoline
antimalarials), quinine continued to be the first
choice to treat malaria in the West. However, quinine
is associated with side effects such as diarrhea. 4-
aminoquinoline antimalarials such as amodiaquine and
28. Antimalarial Drug Discovery: From Quinine to the Dream
of Eradication
During the Vietnam War 1962–1975, there
were 24,606 cases of malaria, an estimated
391,965 sick-days because of malaria, and 46
deaths due to malaria. With the worldwide
resurgence of malaria, the spread of drug-
resistant strains of Plasmodium falciparum, the
emergence of chloroquine-resistant Plasmodium
falciparum
Malaria felled more combatants during the
war than bullets. The disease reduced the
combat strength of some units by half. Over
40,000 cases of Malaria were reported in US
Army troops alone between 1965
Men Against Mosquitoes: Malaria in War | Defense Media
29. The herb, Artemisia annua has been used by Chinese herbalists for over two millennia.
It was not until after the 1970s when the active principle was identified by Chinese
scientists and was called qinghaosu (artemisinin). Clinical studies performed on
members of the Chinese army that are affected by malaria delivered excellent results.
The experiments demonstrated that qinghaosu had excellent therapeutic efficiency.
Most notably, chloroquine-resistant plasmodium falciparum were affected by the
active compound of A. annua
30. The researchers who discovered qinghaosu not only had problems with production and formulation. They were
also restricted from disseminating their findings to the rest of the world. External access to the purified drug was
generally restricted by the Chinese government at the time. Organisations with resources to study A. annua such
as the World Health Organisation (WHO) were denied access to the herb and the drug. The results of the studies
were eventually published on the Chinese Medical Journal where the information became more accessible to
those outside China (Chinese Medical Journal, 1979, 92 (12), pp 811-816).
Bottleneck
31. Many scientists were initially skeptical of artemisinin’s usefulness as
a drug because of the compound’s unstable appearance. The
trioxane ring which contained an endoperoxide bridge was cited to
be an unstable feature. It is now generally believed that the
trioxane ring is central to the compound’s activity.
Drug Design
32. Artemisinin serves as a lead compound for the development of
new antimalarials with improved properties. The therapeutic
utility of the lead itself is limited by poor physicochemical
properties such as water solubility. The lactone group can be
reduced using reducing agents such as sodium borohydride
(NaBH4 ). The reduced form, dihydroartemisinin is used to
prepare semisynthetic prodrug derivatives that are more
water-soluble.
The hydroxyl group can be alkylated to give oilsoluble ether
derivatives such as artemether and arteether. Esterification of
the hydroxyl with succinic acid gives the water-soluble
derivative, artesunate.
Artemether is generally given to patients through
intramuscular injections. Artesunate can be administered
intravenously and orally. Artemisinin semisynthetic derivatives
are often administered alongside other antimalarials to
decrease the likelihood of the development of resistance.
33. The synthesis of analogues, as well as the study of metabolites allowed researchers to investigate
structure-activity relationships. Studies of artemisinin analogues such as deoxyartemisinin which do not
contain the endoperoxide bridge, showed vastly reduced biological activity. In essence, structure-activity
relationships studies of analogues led to the conclusion that the trioxane ring containing the
endoperoxide bridge is part of the pharmacophore and is crucial to antiplasmodial activity
34. Moreover, derivatization at the carbonyl lactone demonstrated that it is a possible region of modification that can be
manipulated in order to improve pharmacokinetic properties. This was demonstrated by the semisynthetic prodrugs.
Compared to artemisinin itself, artemether, artesunate and dihydroartemisinin are more active.
35. Arteflene, which is based on another endoperoxide-containing compound known as
yingzhaosu, exhibited antimalarial activity about half of artemisinin. Arterolane, a
synthetic trioxolane with better pharmacokinetic properties than semisynthetic
artemisinins, is currently in clinical trials.
Artabotrys hexapetalus