A New Class of Coumate Benzimidazole Hybrids as BRCA 1 Mimetics Through Unconventional Binding Mode; Synthesis and Preliminary Cytotoxicity Screening

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Author(s): Selvaraj Jubie*, Neetu Yadav, Shyam Sundar P, Podila Naresh, Ashish Wadhwani, Jawahar Natarajan

Journal Name: Current Computer-Aided Drug Design

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Abstract:

Aims: The present work focus to identify a new class of BRCA-1 mimetics that work differently from conventional anti estrogens.

Background: It was found that breast cancer susceptibility protein1 (BRCA1) binds to estrogen receptor alpha (ERα) and inhibits its activity by direct interaction between domains within the amino terminus of BRCA1 and the carboxy terminus of ER alpha.

Objective: A novel class of hybrids having coumate and benzimidazolone scaffolds were designed to mimic BRCA1 protein, supressing the tumor activity of breast cancer cell.

Method: The in silico molecular docking studies of the designed ligands were performed on BRCA-1 binding cavity of ER alpha. The designed hybrids which have given significant docking scores and having optimum binding interactions with key residues been selected for synthesis and in-vitro assay.

Result: The compounds NY1 and NY2 exhibited significant effects on suppressing MDA-MB-231 cells in the concentration of 24 µg/ml and 44 µg/ml respectively.

Conclusion: The developed coumate-benzimidazolone hybrids may act as Leads as BRCA-1 mimetics.

Other: However,to explore their BRCA-1 mimetics potential, additional experimental data are needed.

Keywords: Breast Cancer, Scaffold, BRCA1, Coumate, Benzimidazolone, ERα

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Article Details

(E-pub Ahead of Print)
DOI: 10.2174/1573409916666191231102046
Price: $95

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