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

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 Molecul...

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Autores principales:	Yousuf Z, Iman K, Iftikhar N, Mirza MU
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Breast cancer HSP90 HER2 EGFR Virtual screening Molecular Docking ADMET Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/44dabbec68634c82816130e465179c9a
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spelling	oai:doaj.org-article:44dabbec68634c82816130e465179c9a2021-12-02T04:50:57ZStructure-based virtual screening and molecular docking for the identification of potential multi-targeted inhibitors against breast cancer1179-1314https://doaj.org/article/44dabbec68634c82816130e465179c9a2017-06-01T00:00:00Zhttps://www.dovepress.com/structure-based-virtual-screening-and-molecular-docking-for-the-identi-peer-reviewed-article-BCTThttps://doaj.org/toc/1179-1314Zeeshan 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 proteinsYousuf ZIman KIftikhar NMirza MUDove Medical PressarticleBreast cancerHSP90HER2EGFRVirtual screeningMolecular DockingADMETNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBreast Cancer: Targets and Therapy, Vol Volume 9, Pp 447-459 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Breast cancer HSP90 HER2 EGFR Virtual screening Molecular Docking ADMET Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Breast cancer HSP90 HER2 EGFR Virtual screening Molecular Docking ADMET Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yousuf Z Iman K Iftikhar N Mirza MU Structure-based virtual screening and molecular docking for the identification of potential multi-targeted inhibitors against breast cancer
description	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
format	article
author	Yousuf Z Iman K Iftikhar N Mirza MU
author_facet	Yousuf Z Iman K Iftikhar N Mirza MU
author_sort	Yousuf Z
title	Structure-based virtual screening and molecular docking for the identification of potential multi-targeted inhibitors against breast cancer
title_short	Structure-based virtual screening and molecular docking for the identification of potential multi-targeted inhibitors against breast cancer
title_full	Structure-based virtual screening and molecular docking for the identification of potential multi-targeted inhibitors against breast cancer
title_fullStr	Structure-based virtual screening and molecular docking for the identification of potential multi-targeted inhibitors against breast cancer
title_full_unstemmed	Structure-based virtual screening and molecular docking for the identification of potential multi-targeted inhibitors against breast cancer
title_sort	structure-based virtual screening and molecular docking for the identification of potential multi-targeted inhibitors against breast cancer
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/44dabbec68634c82816130e465179c9a
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Structure-based virtual screening and molecular docking for the identification of potential multi-targeted inhibitors against breast cancer

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