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Structure-based virtual screening and molecular docking for the identification of potential multi-targeted inhibitors against breast cancer

Authors Yousuf Z, Iman K, Iftikhar N, Mirza MU

Received 17 January 2017

Accepted for publication 3 May 2017

Published 14 June 2017 Volume 2017:9 Pages 447—459

DOI https://doi.org/10.2147/BCTT.S132074

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Professor Pranela Rameshwar

Zeeshan Yousuf,1 Kanzal Iman,1 Nauman Iftikhar,2 Muhammad Usman Mirza3,4

1Institute of Molecular Biology and Biotechnology, The University of Lahore, Lahore, 2National Institute for Genomics and Advanced Biotechnology, National Agricultural Research Centre, Islamabad, 3Centre for Research in Molecular Medicine, The University of Lahore, Lahore, Pakistan; 4Medicinal Chemistry, Department of Pharmaceutical and Pharmacological Sciences, Rega Institute for Medical Research, University of Leuven, Leuven, Belgium

Abstract: Breast cancer is characterized by an uncontrolled growth of cells in breast tissue. Genes that foster cell growth in breast cells are overexpressed, giving rise to breast tumors. The identification of effective inhibitors represents a rational chemopreventive strategy. The current in silico study provides a pharmacoinformatic approach for the identification of active compounds against a co-chaperone HSP90 and the human epidermal growth factor receptors EGFR and HER2/neu receptor. The elevated levels of expression of these target proteins have been documented in breast cancer. The utilization of drug-likeness filters helped to evaluate the pharmacological activity of potential lead compounds. Those fulfilling this criterion were subjected to energy minimization for 1000 steepest descent steps at a root means square gradient of 0.02 with an Amber ff12SB force field. Based on molecular docking results and binding interaction analysis, this study represents five chemical compounds (S-258282355, S-258012947, S-259417539, S-258002927, and S-259411474) that indicate high binding energies that range between −8.7 to −10.3 kcal/mol. With high cytochrome P inhibitory promiscuity activity, these multi-targeted potential hits portray not only good physiochemical interactions but also an excellent profile of absorption, distribution, metabolism, excretion, and toxicity, which hypothesizes that these compounds can be developed as anticancer drugs in the near future.

Keywords: EGFR, metastasis, TNBC, HER2, heat shock proteins

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