Disadvantages Of Cadd

TO DESIGN AND PERFORM IN SILICO STUDIES OF 3-(6'-SUBSTITUTED HEXYLOXY) 1-HYDROXY XANTHONE DERIVATIVES AGAINST PROTEIN 3LN1 AS COX-2 INHIBITORS.

INTRODUCTION TO COMPUTER AIDED DRUG DESIGN

CADD is capable of increasing the hit rate of novel drug compounds because it uses a much more targeted search than traditional HTS and combinatorial chemistry. It not only aims to explain the molecular basis of therapeutic activity but also to predict possible derivatives that would improve activity. In a drug discovery campaign, CADD is usually used for three major purposes:

i. Filter large compound libraries into smaller sets of predicted active compounds that can be tested experimentally ii. Guide the optimization of lead compounds, whether to increase

Virtual screening, lead optimization and prediction of bioavailability and bioactivity may help to guide the research and development programme.

b) Time-to-Market: - The prediction power of CADD (Computer Aided Drug Design) may help drug research programs to choose only the most appropriate drug candidates. By focussing on drug research on specific lead candidates and avoiding potential “dead end” compounds, pharmaceutical companies can get drug to market more quickly.

c) Insight:- One of the non-quantitative benefits of CADD and the use of bioinformatics tools is that researchers acquire information about drug receptor interactions. When we show researchers new molecular models of their putative drug compounds, their protein targets and how they binds together; they often come up with new ideas how to modify the drug compounds for improved fit. This is a tangible benefit that can help researcher to design research programmes (Agarwal et al., 2013).

 Ligand prepration

 Protein prepration

 Protein-ligand docking study

 Binding energy

Incorporation of amine-terminated alkoxy side chains at the 3rd and 6th positions of the xanthone enhances COX-2 inhibitory activity (Chen et al., 2007)

BASIC STRUCTURE FOR WHOLE SERIES

Fig3: Pentyl chain substituted 1,3 dihydroxy xanthone nucleous

Where X=primary or secondary amines e.g. 2-methyl piperidine, 2-amino pyridine,

4-nitroaniline etc.

MATERIALS AND METHOD

Library of a series named as series B with 24 compounds were designed and subjected for pre screening studies like finding logp, violations, drug score, toxicity and mutagenicity etc. with the help of software Molinspiration and DataWarrior. In-silico Docking study was carried out by using Discovery Studio 4.5, where Celecoxib was taken as standard drug. Protein 3ln1 was downloaded from RCSB Protein Data Bank and ligands were prepared by using Chem Draw. The best five binding interactions based upon the binding energies are recorded and reported below along with their 2D images.

LIST OF AMINES USED AS SUBSTITUENT

List of amines substituted in side chain of xanthone nucleous to produce xanthone derivatives and these derivatives will be docked in the protein binding