Chalcone derivatives: In silico design, molecular docking study and anticancer activity on MCF-7 cells

Chalcones, a class of naturally occurring flavonoid compounds, have been reported to possess various biological activities, including anticancer properties. In this study, a series of chalcone derivatives were designed using computational tools to explore their potential as inhibitors of cancer cell growth. The molecular docking technique was employed to predict the binding affinities and interaction modes of these derivatives with key cancer-related target proteins, such as the estrogen receptor and various kinases involved in cancer cell proliferation and survival. In-silico methods were used to develop and evaluate 35 substituted chalcone derivatives. For their physicochemical, toxicological, and binding energies with 5 proteins 2OWB, 2QTU,3ERT,3IKA and 6GU7 in comparison with a standard Docetaxel.The docking studies revealed several chalcone derivatives with promising binding affinities and interactions, Compound D31 showed the highest docking score of –338.4398 kcal/mol, indicating the strongest inhibitory potential among the tested compounds and Compound D16 displayed a docking score of –304.7387 kcal/mol, suggesting their potential as effective inhibitors. In parallel, the chalcone derivatives were synthesized by combining an aromatic aldehyde and an aromatic ketone using Claisen Schmidt condensation where D22 had the highest yield (89.00%) among the synthesised compounds, followed by D15 (80.57%), D16 (75.70%), D31 (30.66%), and D7 (24.64%). and evaluated for their cytotoxic activity against MCF-7, a human breast cancer cell line. Cell viability assays, such as MTT, were performed to assess the cytotoxic effects of the chalcone derivatives, with compound D16 exhibited a dose-dependent cytotoxic effect, achieving notable inhibition of MCF-7 cell proliferation at 500 µg/mL, with an IC₅₀ value of 312.84 µg/mL.exhibiting significant antiproliferative effects, comparable to or even exceeding those of standard chemotherapeutic agents. Overall, the study highlights the potential of chalcone derivatives as promising anticancer agents and underscores the utility of in silico methods for the rational design and optimization of novel anticancer compounds.