A COMPARATIVE GROUP-QSAR AND MOLECULAR DOCKING STUDIES OF 4 -THIAZOLIDINONE CONTAINING INDOLIN-2-ONE MOIETY AS VGEFR INHIBITORSAbstract
Vascular endothelial growth factor receptors (VEGFR) are kinase based receptors reported as a promising target in anti tumour therapy. VGEFR inhibitors are being investigated which can have important contribution in anti-angiogenic therapy for treatment of cancer. In the present study, an attempt has been made to develop a site-specific QSAR model in order to explore the definite sites of substitution of a series of 4-thiazolidinone derivatives having reported antitumor activity against h460 cell lines. Each molecule of the series was divided into seven fragments for varying substituent at the positions R1, R2, R3, R4, R5, R6 and R7 of the parent nucleus. GQSAR was performed using MLR, PCR, PLS and KNN methods of variable selection. Amongst these methods, PCR has come out with promising result as compared to other methods. A comparative docking study was performed to explore the particular sites of interactions within the binding cavity of VGEFR protein. (PDB id: 1Y6A). The important substitutions contributing towards the biological activity by interpreting the developed GQSAR equation using virtual studies were found out which are as follows. position R1 should be substituted with groups with low electro negativity and higher atomic mass , oxygen count at R5 should be increased which would act as hydrogen bond acceptors and total polar surface area at R7 has to be decreased by making substitutions of non polar groups to promote hydrophobic interactions.
Pragya Nayak * and Monica Kachroo
Department of Pharmaceutical Chemistry, Al-Ameen College of Pharmacy, Bangalore, Karnataka, India.
27 September, 2016
29 November, 2016
08 January, 2017
01 April, 2017