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

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

Journal Name: Current Computer-Aided Drug Design

Volume 16 , Issue 6 , 2020

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Graphical Abstract:


Background: It was found that breast cancer susceptibility protein 1 (BRCA 1) binds to estrogen receptor alpha (ERα) and inhibits its activity by direct interaction between domains within the amino terminus of BRCA 1 and the carboxy terminus of ER alpha.

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

Methods: A novel class of hybrids having coumate and benzimidazolone scaffolds were designed to mimic BRCA 1 protein, suppressing the tumor activity of breast cancer cells. In silico molecular docking studies of the designed ligands were performed on BRCA 1 binding cavity of ER alpha.

Results: The designed hybrids which gave significant docking scores and had optimum binding interactions with key residues were selected for synthesis and in vitro assay.

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

Keywords: Breast cancer, scaffold, BRCA1, coumate, benzimidazolone, ERα.

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Article Details

Year: 2020
Published on: 18 January, 2021
Page: [786 - 801]
Pages: 16
DOI: 10.2174/1573409916666191231102046
Price: $65

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