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International Journal of Medicinal Chemistry
Volume 2014, Article ID 658016, 15 pages
http://dx.doi.org/10.1155/2014/658016
Research Article

Target Based Designing of Anthracenone Derivatives as Tubulin Polymerization Inhibiting Agents: 3D QSAR and Docking Approach

1Department of Pharmaceutical Chemistry, College of Pharmacy, Salman bin Abdul Aziz University, P.O. Box 173, Al-kharj 11942, Saudi Arabia
2Faculty of Pharmacy, University of Sydney, NSW 2006, Australia
3Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Ferozepur Road, Moga 142 001, India
4Department of Pharmacology, College of Pharmacy, Salman bin Abdul Aziz University, P.O. Box 173, Al-kharj 11942, Saudi Arabia

Received 31 August 2013; Revised 17 February 2014; Accepted 25 February 2014; Published 17 April 2014

Academic Editor: Arie Zask

Copyright © 2014 Abdul Samad et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Novel anthracenone derivatives were designed through in silico studies including 3D QSAR, pharmacophore mapping, and molecular docking approaches. Tubulin protein was explored for the residues imperative for activity by analyzing the binding pattern of colchicine and selected compounds of anthracenone derivatives in the active domain. The docking methodology applied in the study was first validated by comparative evaluation of the predicted and experimental inhibitory activity. Furthermore, the essential features responsible for the activity were established by carrying out pharmacophore mapping studies. 3D QSAR studies were carried out for a series of 1,5- and 1,8-disubstituted10-benzylidene-10H-anthracen-9-ones and 10-(2-oxo-2-phenylethylidene)-10H-anthracen-9-one derivatives for their antiproliferation activity. Based on the pattern recognition studies obtained from QSAR results, ten novel compounds were designed and docked in the active domain of tubulin protein. One of the novel designed compounds “N1” exhibited binding energy −9.69 kcal/mol and predicted Ki 78.32 nM which was found to be better than colchicine.