Structure-based pharmacophore design and virtual screening for novel potential inhibitors of epidermal growth factor receptor as an approach to breast cancer chemotherapy

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 IC[Formula: see text] values 327 and 370 nM, respectively.

Molecular Docking and Biophysical Studies for Antiproliferative Assessment of Synthetic Pyrazolo-Pyrimidinones Tethered with Hydrazide-Hydrazones

“…With this regard, a literature survey revealed that molecular docking into the ATP binding site of EGFR (protein data bank ID: 1M17) was a robust strategy for identification of effective EGFR inhibitors endowed with cytotoxic properties [58][59][60]. In the current study, docking simulations using the crystal structure of EGFR, co-crystallized with its inhibitor erlotinib, has been performed to elucidate the interactions of the active cytotoxic agents 5a, 5e, 5g, and 5h at the 'Erlotinib' binding domain of tyrosine kinase enzyme (protein data bank ID: 1M17), by using Autodock 4.2 ( Table 2).…”

Research Article Gold nanoparticle sucrose complexes as potent anti-inflammatory agents

“…Then, cells were washed with PBS before adding MTT solution (20 µL of 5 mg/mL MTT solution per each well). After 4 h, the absorbance of the developed color of each well was measured at 570 nm using a microplate reader (ELx800 Absorbance Microplate Reader, BioTek, Winooski, USA) (Mosayebnia et al, 2014), (Tabasi et al, 2013), (Mahernia et al, 2017).…”