TY - JOUR AU - Kaushik, Swati AU - Rikhi, Megha AU - Bhatnagar, Seema PY - 2015/12/01 Y2 - 2024/03/29 TI - DOCKING AND CYTOTOXICITY STUDIES OF 2-VINYLCHROMONE DERIVATIVES ON HUMAN BREAST CANCER CELL LINES JF - International Journal of Pharmacy and Pharmaceutical Sciences JA - Int J Pharm Pharm Sci VL - 7 IS - 12 SE - Original Article(s) DO - UR - https://journals.innovareacademics.in/index.php/ijpps/article/view/8496 SP - 113-117 AB - <p><strong>Objective: </strong>Estrogen receptor (ER) is over-expressed in 70% of breast cancers. The ER has two isoforms, ERα and ERβ. The ER ligand binding domain (LBD) has been the target for hormone-responsive breast cancer. Due to tissue-specific effects currently available drugs for hormone positive breast cancer presents serious limitation. The dynamic and plastic nature of ER LBD plays a crucial role in ligand design that discriminates between the ER subtypes. Agents that selectively target ER isoform are a formidable challenge to researchers. The chromone scaffold is a privileged scaffold for exploration of anticancer agents. The objective of the present study was to evaluate the anticancer activity of a small library of 2-vinylchromones in human breast cancer cell lines MCF-7 and MDA-MB-231.</p><p><strong>Methods: </strong>The compounds were synthesized by the reported procedures. Docking studies of the substituted 2-vinylchromone was performed using GLIDE tool in Maestro 8.0. The compounds were evaluated for anticancer activity against MCF-7 (ERα positive), MDA-MB-231 (ERβ positive) and MRC-5 (ERα, β negative) cell lines using MTT assay.</p><p><strong>Results: </strong>The <em>in silico</em> studies indicated that substituted 2-vinylchromones, <strong>1(a-c)</strong> and <strong>2(a-b)</strong> exhibited comparable docking score at LBD of ERα and ERβ. However, the binding affinity of the compounds for the allosteric binding site in ERβ was negligible. The dose-dependent studies using MTT assay depicted that compounds <strong>1(a-c)</strong> and <strong>2(a-b)</strong> exhibited anticancer activity in ERα positive cell line MCF-7 as compared to ERβ positive cell line <strong>MDA MB 231.</strong> The most potent anticancer activity was observed for compound <strong>2b</strong> against MCF-7 cells with IC<sub>50</sub> value of 15.625 μg/ml.</p><p><strong>Conclusion: </strong>The present investigation indicated that 2-vinylchromone derivatives exhibited ER isoform selectivity and the presence of bulky group in 2-vinylchromones resulted in significantly higher cytotoxicity in ERα positive cell lines as compared to the ERβ positive cell line.</p><p> </p> ER -