Potential Coumarin Thiosemicarbazone Hybrids as BRCA-1 Mimetics for ER Positive Breast Cancer Therapy: An In-silico Approach

Shyam Sundar P, Podila Naresh, Jawahar Natarajan, Ashish Wadhwani, Selvaraj Jubie*

JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Tamilnadu, India

ABSTRACT

The goal of this study is to find a novel class of BRCA-1 mimics for Estrogen Receptor α (ERα) breast cancer that works differently from conventional anti-estrogens. Breast Cancer Susceptibility Protein-1 (BRCA-1) is a protein was discovered to bind to ERα and decrease its function by a direct contact between regions inside BRCA1's amino terminus and the carboxy terminus of ERα. A novel class of hybrids with coumate and thiosemicarbazone scaffolds was created with the premise of developing small compounds that imitate the function of BRCA-1 to down regulate the ERα and inhibit the tumor activity of breast cancer cells. Using Schrodinger 2020-2, ADMET and in silico molecular docking tests of the proposed hybrids were performed on the BRCA-1 binding cavity of ERα. TSCO-XIV and TSCO-III are developed hybrids that have high docking scores and good binding interactions with important residues.

Keywords:

BRCA-1, Breast Cancer, Scaffold, Coumate, Thiosemicarbazone, ER alpha