INSILICO DRUG DESIGN AND MOLECULAR DOCKING STUDIES OF NOVEL COUMARIN DERIVATIVES AS ANTI-CANCER AGENTS

• Published in: Asian journal of pharmaceutical and clinical research Vol. 10; no. 4; p. 335
• Main Authors: Mehta, Simpi, Pathak, Seema R
• Format: Journal Article
• Language: English
• Published: 01.04.2017
• ISSN: 0974-2441; 0974-2441
• DOI: 10.22159/ajpcr.2017.v10i4.16826

 Objective: Cancer is the major worldwide problem. It arises due to uncontrolled growth of cells. In the present study a series of novel coumarin derivatives were designed and computationallyoptimized to investigate the interaction between designed ligands and 10 pdb files of five selected proteins. The objective here was to analyse in silico anticancerous activity  of designed ligands to reduce cost and time for getting novel anticancerous drug with minimum side effects.Methods: Docking studies were performed to find outmaximum interaction between designed ligands  and  selected five proteins  using Schrondinger software Maestro. Capecitabin has been used as reference compound. Structures of selected proteins were downloaded from protein data bank.Results: All the designed ligands showed mild to excellent binding with proteins.Most of the ligands exhibited better interaction  compared to reference compoundcapacitabin with all pdb files. Some of  designed ligands amongst (1-7) showed excellent docking score with  all pdb files(2v5z, 2v60, 2v61) ofAmine oxidase. Conclusion: All the designed ligands were docked with ten pdb files of five different proteins and it was found that out of seven designed ligand, ligand 4 showed best binding (docking score -10.139 ) with  pdb 2v5z of protein Amine oxidase. Docked ligand cavity of ligand 4 showed  important hydrophobic/non polar residues such asIle199,Ile316,Trp119,Phe168,Ile198,Cys172,Tyr188,Tyr398,Tyr435,Phe343,Tyr60,Leu328,Leu171 and showed pi-pi interaction with Tyr326.Further wet lab studies are continued in our laboratory to  confirm and find out efficiency and activity of target compounds.Keywords: Docking, Mono Amine Oxidase, Coumarin derivatives, Anticancerous activity, binding energy, Ramachandran Plot, Hydrophobic residue.