Editor-in-Chief Hatice Kübra Elçioğlu Vice Editors Levent Kabasakal Esra Tatar Online ISSN 2630-6344 Publisher Marmara University Frequency Bimonthly (Six issues / year) Abbreviation J.Res.Pharm. Former Name Marmara Pharmaceutical Journal
Journal of Research in Pharmacy 2019 , Vol 23 , Issue 6
A facile in silico drug design strategy based on reference listed drugs and computational modeling of novel anticancer therapeutics
Ghansham MORE1,Asha THOMAS1,Sohan CHITLANGE1,Rabindra NANDA1,Manoj DAMALE2
1Department of Pharmaceutical Chemistry, Dr. D.Y. Patil Institute of Pharmaceutical Sciences and Research, Savitribai Phule Pune University, 411018, Pune, India
2Department of Pharmaceutical Chemistry, Srinath College of Pharmacy, Dr. Babasaheb Ambedkar Technological University, 431136, Aurangabad, India
DOI : 10.35333/jrp.2019.71 Heterocyclic compounds present unique structural and physicochemical diversity. Especially, the aromatic heterocycliccompounds like indole exhibit anti-cancer properties by facilitating cancerous cell death. Drug discovery and development process relyto a large extent on the in silico identification of the putative targets and rational design of potentially therapeutic ligands. We propose a facile strategy of in silico drug designing hereby curating libraries having a functional group modification of the indole heterocyclic compounds with 2-chloro-N-(2-chloroethyl)-N-methylethanamine. Subsequently, we compare the designed drugs with the existing alkylating Reference Listed Drugs (RLDs) of the USFDA. We computationally model the indole ring as a basic scaffold and induce 2-chloro-N-(2-chloroethyl)-N-methylethanamine substitution on the C-3 of indole with experimentally available target DNA receptor to design an extensive library of 200 molecules. This was followed by extensive ligand-DNA docking studies to predict putative targets andADMET prediction of an optimized ligand. Our simple in silico strategy reveals that the designed compounds such as AGSPBM134, AGSPBM133, AGSPBM131, AGSPBM130, AGSPBM132 and AGSPBM019 exhibitstructural similarity towards the RLD as shown by ECFP-6 fingerprints. We show that they pass all the similarity criteria of the physicochemical parameters with no violation of the Lipinski’s rule of five. We positthat these agents can potentially be a good choice for further synthesis in the development of novel anti-cancer agents. Keywords : Indole; drug designing; molecular docking; computer-aided drug designing; ADMET
Marmara University