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.
Graphical Abstract
Related Journals
Anti-Cancer Agents in Medicinal Chemistry
Current Analytical Chemistry
Current Bioactive Compounds
Combinatorial Chemistry & High Throughput Screening
Current Medicinal Chemistry
Central Nervous System Agents in Medicinal Chemistry
Letters in Drug Design & Discovery
Current Drug Discovery Technologies
The Natural Products Journal
Current Catalysis
Related Books
Botanicals and Natural Bioactives: Prevention and Treatment of Diseases
Biosurfactants: A Boon to Healthcare, Agriculture & Environmental Sustainability
Frontiers in Computational Chemistry
Advances in Dye Degradation
Biological and Medical Significance of Chemical Elements
Frontiers In Medicinal Chemistry
Advances in Organic Synthesis
Frontiers in Natural Product Chemistry
Recent Advances in Analytical Techniques
Advanced Catalysts Based on Metal-organic Frameworks (Part 2)
24