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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

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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