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Structure-Based Pharmacophore Design and Virtual Screening for Novel Potential Inhibitors of Epidermal Growth Factor Receptor As an Approach to Breast Cancer Chemotherapy Publisher Pubmed



Mahernia S1 ; Hassanzadeh M1 ; Sharifi N1 ; Mehravi B2 ; Paytam F3 ; Adib M3 ; Amanlou M1
Authors
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Authors Affiliations
  1. 1. Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Department of Medical Nanotechnology, Iran University of Medical Sciences, Tehran, Iran
  3. 3. School of Chemistry, College of Science, University of Tehran, Tehran, Iran

Source: Molecular Diversity Published:2018


Abstract

Cancer cells are described with features of uncontrolled growth, invasion and metastasis. The epidermal growth factor receptor subfamily of tyrosine kinases (EGFR-TK) plays a crucial regulatory role in the control of cellular proliferation and progression of various cancers. Therefore, its inhibition might lead to the discovery of a new generation of anticancer drugs. In the present study, structure-based pharmacophore modeling, molecular docking and molecular dynamics simulations were applied to identify potential hits, which exhibited good inhibition on the proliferation of MCF-7 breast cancer cell line and favorable binding interactions on EGFR-TK. Selected compounds were examined for their anticancer activity against the Michigan Cancer Foundation-7 (MCF-7) breast cancer cell line which overexpresses EGFR using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay. Compounds 1 and 2, with an isoindoline-1-one core, induced significant inhibition of breast cancer cells proliferation with IC50 values 327 and 370 nM, respectively. © 2017, Springer International Publishing AG, part of Springer Nature.
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