The document summarizes a study on computer aided drug design of ligands that inhibit 5-hydroxytryptamine 2A (5-HT2A) receptors. The study used software to virtually screen ligands and identify those with the highest binding affinity to the receptors. A novel ligand, 4-(5H-Dibenzo[a,d]cycloheptene-5-ylidene)-1,4-pyrazine, was found to have the best binding affinity of -8.6 kcal/mol to the receptors. This ligand has potential as a new 5-HT2A antagonist for treating conditions like hypertension.

1. COMPUTER AIDED DRUG DESIGN
BY
MR.JITENDRA N.BHALAVI
(D.PHARM, B.PHARM)
PRIYADARSHINI J.L.COLLEGE OF PHARMACY

2. INDEX
 INTODUCTION-----------------------------------------------------2
I. Drug Design----------------------------------------------------2
II. Computer aided drug design-------------------------------2
 5-HYDROXYTRYPTAMIN-2A RECEPTORS----------------3
 AIM &OBJECTIVE-------------------------------------------------4
 RESULT & DISCUSSION------------------------------------------6
 CONCLUSION -------------------------------------------------------7
 REFFERENCE ------------------------------------------------------8
 THANK YOU --------------------------------------------------------9
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3. 1.INTRODUCTION
1.1 DRUG DISCOVERY
The process of drug discovery involves involves the identification of lead molecule,synthesis,characterization,screening and assay of therapeutic activity
fig.1.process of drug discovery
1.2 Computer Aided Drug Design
 various approaches of CADD arae evaluated as promising techniques
according to their need, in between all these structure based drug design. Its very
efficient and powerful technique in drug discovery and development process
fig.2.Graphical abstract of CADD
fig.1.diagram of drug discovery
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4. 2.-HYDROXYTRYPTAMINE-2A RECEPTORS:
5-HT2a receptors is the most widely expressed postjunctional 5-HT receptor
located on vascular and visceral smooth muscle,platelets cerebral neurones. It
mediates most of direct actions of 5-HT like vasoconstrictions,
intestinal,uterine, and bronchial contraction, platelets aggregation .
Fig.3.diagram of 5-HT2a receptors
2.1.Mechanism of action of 5-HT2a receptor :
5-HT2a receptor are couple to Gq protein to activate phospholipase C and
function through generation of IP3/DAG. 5-HT2a receptor also inhibit K channel
resulting is slow depolarization of neurones.
fig.4. mechanism of action of 5-HT2a receptors 3

5. 3.AIM:
 To Screening of Biologically Active Ligands as 5-HT2a Receptor Inhibitor
3.1 Objective:
To Find Out Best Ligand Showing Good Receptor Binding Affinity
4.PLAN OF WORK:
DOWNLOAD
ING OF
SOFWARE
PROGRAM
PREPRATION
OF LIGAND
PREPRATI
ON OF
RECEPTOR
S
VIRTUAL
SCREENING
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6. 5.EXPERIMENTAL WORK:
Software and programs:
chemsketch a structure drawing
tool, pyrex used for virtual
screening
Prepration of Ligand :
Ligand structure was drawn by
chemsketch and a set of 3 ligand
was prepared
Prepration of Receptors:
The structure was downloaded
in pdb.format
i.e.4oaj5HT2a.pdb.format
Virtual screening:
The pyrex software was used for
virtual screening
By using this 4 step the
experimrntal work was carried
out
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7. 6.RESULT & DISCUSSION:
Table of total screening molecule with their structure, IUPAC Name, and
binding affinity
Sr.no. Name of molecule Structure
Binding
affinity
(kcal/mol)
1.
4-(5H-
Dibenzo[a,d]cycloheptene-
5-ylidene)-1,4-pyrazine
-8.6
2. Pyrazine -3.2
3. cyproheptadine -8.1
N
N
NH
N
H
N
CH3
After performing virtual screening of different molecule with active ligand as 5-
HT2a recptors inhibitor the dibenzocycloheptenes and pyrazine derivative showed
better binding affinity than other molecules.
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8. The 4-(5H-Dibenzo[a,d]cycloheptene-5-ylidene)-1,4-pyrazine a novel 5-HT2a
antagonist this molecule had the best binding affinity of -8.6kcal/mol
Fig.5.2D Structure of novel 5-HT2a
Antagonist
7.CONCLUSION:
 The study showed novel 5-HT2a antagonist i.e 4-(5H-
Dibenzo[a,d]cycloheptene-5-ylidene)-1,4-pyrazine having potent
antihypertensive, antiashthamatic, antiplatelet aggregation action. The
result revealed binding affinity as -8.6 kcal/mol and interaction with active
sites. This helped us to confirm the potency of the molecule towards
receptors responsible for the treatment of hypertension.
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9. 7.REFFERENCE:
Drews, J. (2000). Drug discovery: a historical perspective. science, 287(5460),
1960-1964.
Anderson, Amy C. "The process of structure-based drug design." Chemistry
& biology 10, no. 9 (2003): 787-797.
Frank, Guido K., Walter H. Kaye, Carolyn C. Meltzer, Julie C. Price, Phil
Greer, Claire McConaha, and Kelli Skovira. "Reduced 5-HT2A receptor
binding after recovery from anorexia nervosa." Biological Psychiatry 52, no. 9
(2002): 896-906.
Åqvist, Johan, Carmen Medina, and Jan-Erik Samuelsson. "A new method
for predicting binding affinity in computer-aided drug design." Protein
Engineering, Design and Selection 7, no. 3 (1994): 385-391.
Wadood, A., et al. "In-silico drug design: An approach which
revolutionarised the drug discovery process." OA Drug Des Deliv 1.1 (2013): 3.
Wadood, A., Ahmed, N., Shah, L., Ahmad, A., Hassan, H., & Shams, S.
(2013). In-silico drug design: An approach which revolutionarised the drug
discovery process. OA Drug Des Deliv, 1(1), 3.
Åqvist, Johan, Carmen Medina, and Jan-Erik Samuelsson. "A new method
for predicting binding affinity in computer-aided drug design." Protein
Engineering, Design and Selection 7.3 (1994): 385-391.
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10. THANK YOU
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