The document presents research on the synthesis and characterization of various heterocyclic derivatives, particularly focusing on chalcones, pyrazolines, and isoxazolines as potential antioxidant agents. Methodologies, including catalytic studies and docking analyses, demonstrate the biological activities of these compounds, revealing moderate to good antioxidant capability and strong binding energies to targeted enzymes. Findings indicate that several synthesized derivatives possess favorable pharmaceutical properties, suggesting their potential for therapeutic applications.

1. WELLCOME
TO
ALL

2. CATALYTIC SYNTHESIS, CHARACTERIZATION, DOCKING STUDY
AND ADMET PARAMETERS OF SOME HETEROCYCLIC DERIVATIVES
AS POTENT ANTIOXIDANT AGENTS
Presented by
G PRABAKARAN
Dr. S. MANIVARMAN
Assistant Professor, Department of Chemistry
Government Arts College,
C.Mutlur, Chidambaram – 608 102

3. INTRODUCTION

4. Numerous manufactured medications and colours, as well
as various chemicals including alkaloids, antibiotics, vital
amino acids, vitamins, haemoglobin, or hormones, all have
heterocyclic rings as their major structural components
Chalcons have bactericidal, antifungal, insecticide
activity, and are reported to be antimutagenic chalcones
their biological activity is also employed with a variety of
heterociclic molecules, including flavones, flavonols,
pyrazol, isoxazole, thiazine, Oxopyrimidine, and
thiopyrimidine. Therefore, chalcones are considered the
most significant synthesis molecules for a number of
heterocyclic systems

5. Numerous pyrazoline compounds are said to have a
variety of biological properties, including antibacterial,
anti-depressant, neuroprotective, anticonvulsant, anti-
inflammatory, analgesic, antitiscin, local anaesthetic,
hypoglycemia, hypotensive, insecticide, herbicide, and
molluscicidal effects
Pharmaceutical and agrochemical agents, five member
heterocycles such as isoxazoline were widely used. The
synthesis of isoxazoline derivatives as a source of new
antibacterial agents has been given increasing attention in
recent years.

6. Pyrimidines are acknowledged as particularly essential
heterocycles due to their biological characteristics and
therapeutic significance.
It has been shown from the literature studies above that the
main attraction for researchers in the fields of synthetic
organic chemistry are five component heterocyclics,
especially isoxazoline, pyrazolins, pyrimidine and related
compounds.

7. LITERATURE SURVEY

8.  Anti-inflammatory
 Insecticidal
 Antiepileptic
 Antitumor
 Anticancer
 Antiviral
 Herbicidal
 AntiHIV
Based on Literature survey Chalcone, Pyrazoline,
isoxazoline and pyrimidine derivatives show
following biological activities
 Antibacterial
 Antifungal
 Antidiabetic
 Antipyeretic
 Antioxidant
 Antitubercluosis
 Antimalarial
 Analgesic

9. EXPERIMENTAL METHODS
This chapter provides information to experimental methods, All
chemicals were obtained from commercial sources and used
without any further purification.
All the melting points were determined by digital melting point
apparatus.
IR spectra were recorded in Shimadzu FT-IR-8400 instrument
using KBr pellet method.
The 1H NMR spectral data were recorded on Bruker AV 400 MHz
in DMSO and CDCl3 using TMS as an internal standard.
The purity of the synthesized compounds was ascertained by
TLC using iodine vapour as visualizing agents

10. RESULTS AND DISCUSSION

11. SYNTHESIS AND CHARACTERIZATION OF HYDRAZIDE
DERIVATIVE
General procedure for the synthesis (E)-N'-(1-(5-
chlorothiophen-2-yl) ethylidene)furan-2-carbohydrazide
The solution of isonicotinic acid hydrazide (0.01 mol) and
appropriate substituted acetophenone (0.01 mol) in ethanol
was refluxed for 4–5 h. The precipitates obtained were
filtered off, washed, and recrystallized from ethanol.

12. SYNTHESIS AND CHARACTERIZATION OF ALDEHYDE
DERIVATIVE
General procedure for the synthesis of 3-(5-chlorothiophen-2-yl)-1-
(furan-2- carbonyl)-2,3-dihydro-1H-pyrazole-4-carbaldehyde
(E) - N‘ - (1-(5-chloro thiophen-2-yl) ethylidene) furan-2-carbohydrazide)
(3 mmol) was added to the Vilsmeier-Haack reagent made from DMF
(10 mL) and POCl3 (1.1 mL), which was then agitated at 60–65 oC for 2.5
hours before being emptied into ice cold water. The NaHCO3 solid that
separated after neutralisation was filtered, water rinsed off of it, and
column chromatography was used to purify it.

13. SYNTHESIS AND CHARACTERIZATION OF CHALCONE
DERIVATIVE
Synthesis of (E)-3-(3-(5-chlorothiophen-2-yl)-1-(furan-2-carbonyl)-2,3-
dihydro-1H-pyrazol-4-yl)-1-(substituted)prop-2-en-1-one (6a-g)
A solution of 3-(5-chloro thiophen-2-yl)-1-(furan-2-carbonyl)-2,3-
dihydro- 1H-pyrazole-4-carbaldehyde (1mmol) and Acetyl substituted
compounds (1mmol), sodium hydroxide (0.5g) and 10 ml of ethanol in
the presence of TiO2- ZnS nanocatalyst were shaken occasionally for 15
min. After the completion of the reaction, the mixture was cooled at
room temperature. The resulting precipitate was filtered and washed
with cold water.

15. In order to get effective results, the reaction conditions were optimized.
For this purpose, 1-benzoyl-3-(thiophen-2-yl)-2,3-dihydro-1h-pyrazole-4-
carbaldehyde (4) and thiophen-2-carbohydrazide (5b) were used as the
model substrate for the synthesis of substituted chalcone
CATALYTIC STUDIES USING TiO2-ZnS NANOPARTICLES

16. The polar solvents produced better results than non - polar
ones and achieved the best results in ethanol, which most
efficiently managed to eliminate the desired product by means
of the TiO2- ZnS nanoparticles catalyst. All reactions were
carried out smoothly and within 15 min the reaction was
finished to provide good yields (85– 89 percent).
EFFECT OF SOLVENT

17. SUPERIORITY OF TIO2-ZnS NANOPARTICLES OVER SOME OTHER
METAL OXIDE NANOPARTICLES
Different catalysts were used to determine the catalyst's capability
and efficiency. Initially, in the absence of any catalyst the model
reaction was performed, and the response was very slow and the
expected product was very small. When Bare TiO2, commercial
TiO2, bulk TiO2 and bare ZnS, the reaction was examined with
nanoparticles with 7 mol% of each catalyst separately, the reaction
took longer time for completion with higher yield. The reaction with
TiO2-ZnS nanoparticles has been speeded up and the desired
product yield has been maximized.

18. EFFECT OF CATALYST LOADING
The effect of catalyst loading on the model reaction synthesis was
investigated with a variation of 3 to 12 mol%. In order to achieve
optimum results in less response time, it was found that 7 mol% of
the catalyst was necessary, while less than 7 mol% of the catalyst
increased the response times and reduced yield

19. REUSABILITY OF CATLYST
The catalyst had been regenerated with filtering, washed
with dichloromethane and methanol and dried at 150 C
for 4 hours after completion of the model response at a
certain period of time, and then used for the following
cycle. The results indicate that the catalyst has shown up
to five cycles of good catalytic activity.

20. PHYSICAL PROPERTIES OF SYNTHESIZED CHALCONE DERIVATIVES
(6a-g)

21. The strong absorption stretching frequency band appeared at 1660 cm-1 is due to
C=O of chalcone moiety and a stretching frequency band strongly appeared at
1462 cm-1 is due to CH=CH of the chalcone. The stretching frequency band present
in the region of 1595 cm-1 is due to C=N bond. Stretching frequency range at 3049
cm-1 is reveals that the presence of aromatic C-H group. The absence of aliphatic
C-H stretching frequency range at 2900 cm-1 is confirmed the reactant was totally
converted into the product.
IR SPECTRUM OF COMPOUND 6a

22. The strong singlet appeared at 8.12 ppm is due to ring CH proton. The H-
α and H-β protons of chalcones occur as two doublets in the ranges 7.54
ppm (H- α) and 7.91 ppm (H- β) in the 1H NMR spectra.
1H NMR SPECTRUM OF COMPOUND 6a

23. The carbonyl carbon of the chalcones usually appears δ 188.7 in its 13C NMR
spectrum. The α- and β- carbon atoms with respect to the carbonyl group give rise
to characteristic signals in between δ 126.4 and δ 137.4 respectively. Phenyl ring
aromatic carbon signals are appeared from 111.7-158.7ppm. IR, 1HNMR, 13 C
NMR spectrum of other compounds also taken and discussed in the thesis.
13C NMR SPECTRUM OF COMPOUND 6a

24. The majority of the compounds had moderate to good antioxidant activity when
compared to that of common compounds (ascorbic acid). All of the other
compounds under investigation, with the exception of compound 6a (IC50 >150
g/mL), were found to be moderately active, with IC50 values ranging from 76.5 to
119.1 g/mL.
Antioxidant activity of compounds 6a-g

25. Of these, compound 6f (methylenedioxy group) showed almost equal
activity (IC50 =82.8 g/mL), when compared to compounds with compound
6g. Therefore, the hetero atom of oxygen has been significantly involved in
the suppression of antioxidant function. The activities of all the compounds
were compared to those of the positive control, ascorbic acid (IC50 = 34.51
g/mL).

26. Auto Dock 4.2.6 is used perform docking analysis . Auto
Dock Tools (ADT) is used to prepare protein. All water and
hetero- molecules were removed from protein preparation.
Other essential ions were introduced. Kollman charges were
used. Synthesized derivatives were docked with the active
site of α-glucosidase (PDB ID: 2ZEO) and cyclin-dependent
kinase 2 (PDB ID: 1HCK) enzymes.
The SWISS ADMET predictor was used to conduct the
ADMET investigation.
DOCKING STUDIES

27. Docking studies' findings suggest that molecules 6c and 6f have binding
energy(-7.8and7.6kcal.mol-1). Contrarily, compound 6a has a lower
binding energy (-6.2) than compound 6c due to the substituent effect,
which lowers the binding energy. Additionally, the binding energy of the
fluorine substituted molecule 6b is -7.0 kcal.mol-1.
DOCKING EXPERIMENTS WITH THE 1HCK RECEPTOR (6a-g)

28. Docking results of synthesized chalcone derivatives with 1HCK receptor

29. Docking results of synthesized chalcone derivatives with 1HCK receptor

30. Binding score and ic50 value of chalcone derivatives
(6a-g) with 1HCK protein receptor

31. According to the findings of docking experiments, molecules 6a and 6e
have a binding energy of -8.3 kcal.mol-1 for the 2ZE0 receptor.
Compound 6d also has a binding energy of -7.8 kcal.mol-1
DOCKING EXPERIMENTS WITH THE 2ZE0 RECEPTOR (6a-g)

32. Docking results of synthesized chalcone derivatives with 2ZE0 receptor

33. Docking results of synthesized chalcone derivatives with 2ZE0 receptor

34. Binding score and ic50 value of chalcone derivatives
(6a-g) with 2ZE0 protein receptor

35. • The in vitro PPB affinity values in the range of 100.00% confirm
that they are with poor binding capability towards the plasma
proteins, compared to the ascorbic acid
• The %HIA identified is competent with as they are in the range
of 96.67 to 99.90 and are better than standard ascorbic acid with
33.15% and assures their interactions with the reactive species
in the expecting target of domains.
• partition co-efficient (logP) values ranging from 3.08 to 5.45
which are less than 5. These results confirm that 6a-g are with
good pharmaceutical parameters with zero Lipinski property
violations. TPSA have calculated the total polar surface area
and the obtained values are ranging from 62.55 to 78.01 which
are less than 140, number of rotatable bonds are ranging from 5
which are less than 10 authorizes them as potent molecules with
zero Veber property violations to interact with the target cells.
ADMET,QSAR AND BIOACTIVITY PROPERTIES
OF SYNTHESIZED DERIVATIES 6a-g

36. ADMET PROPERTIES OF SYNTHESIZED
DERIVATIES 6a-g

37. QSAR PROPERTIES OF SYNTHESIZED
DERIVATIES 6a-g

38. BIOACTIVITY PROPERTIES OF SYNTHESIZED
DERIVATIES 6a-g

39. • The other properties like Van der Waals volume ranging from
330.68 to 354.6 and solubility ranging from poor to moderate
supports the interaction of ligand molecules with the hosting
receptors and their competent affinity towards the target cells
within the binding domain.
• In the toxicity risk assessment, we have evaluated the drug-likeness
and drug score properties and found that all the compounds are in
the range of 5.46 to 6.35 of the drug-likeness property and is
comparable with the standard ascorbic acid having 0.02 of drug-
likeness property. Similarly, the drug score is in the range of 0.78 to
0.87 which are in comparable to the standard with 0.75 of drug
score.
ADMET,QSAR AND BIOACTIVITY PROPERTIES
OF SYNTHESIZED DERIVATIES 6a-g

40. Acknowledgments
I Thank My Research Guide
Dr. S. MANIVARMAN
Assistant Professor, Department of Chemistry
Government Arts College,
C.Mutlur, Chidambaram – 608 102

41. THANK YOU