Title: 3D-QSAR (CoMFA, CoMSIA) and molecular docking studies of natural flavonoid derivatives to explore structural requirements for MCF-7 cell line inhibition
Authors: Shravan Kumar Gunda; Manasa Reddy Gummi; Jaheer Mohmed; Ayub Shaik
Addresses: Bioinformatics Wing, Mycology and Plant Pathology Lab, Department of Botany, Osmania University, Hyderabad 500007, India ' Bioinformatics Wing, Mycology and Plant Pathology Lab, Department of Botany, Osmania University, Hyderabad 500007, India ' Department of Chemistry, University College of Science, Osmania University, Hyderabad, 500007, India ' Department of Chemistry, University College of Science, Osmania University, Hyderabad, 500007, India
Abstract: In the present study, molecular modelling studies have been reported on a series of natural flavonoid derivatives to analyse structure activity relationship studies of MCF-7 inhibitors using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA)-based QSAR methods. Eighty-four compounds were used as training set to establish the model and 20 compounds were used as external test set to validate these models. The generated models exhibited good statistical results such as q2, r2. CoMFA analysis yielded the q2 of 0.765 and r2 of 0.968 with five components. CoMSIA model generated using steric, electrostatic, hydrophobic, donor and acceptor fields with q2 value of 0.592 and r2 value of 0.932 with six components was found to be the optimal model among the various models generated. According to contour map results, we have recommended the critical sites for modification in structure which will be useful in designing potent compounds with improved activity.
Keywords: flavonoids; MCF-7; CoMFA; comparative molecular field analysis; CoMSIA; comparative molecular similarity indices analysis; molecular docking.
International Journal of Computational Biology and Drug Design, 2017 Vol.10 No.3, pp.264 - 285
Received: 26 Oct 2016
Accepted: 21 Mar 2017
Published online: 25 Jul 2017 *