Synthesis, Cytotoxicity Assay, and Network Pharmacology of 2-Acetylthiophene-based Chalcone Epoxide Derivatives as Anticancer Agents

A series of 2-acetylthiophene-based chalcone epoxides, their activity assays against cancer cells, and network pharmacology studies have been conducted. The synthesis of chalcone epoxides 3a-d afforded solid products in yields ranging from 56% to 91%. Biological screening revealed that compound 3c , with a 4-chloro substituent, is the most promising candidate, with IC 50 = 6.30 and 4.80 µg/mL against HeLa and T47D, respectively. In contrast, 3d with a 4-bromo substituent is the most promising candidate against the WiDr colorectal cancer cell line, with an IC 50 of 2.22 µg/mL. Proteins that potential chalcone epoxides may target have been identified through bioinformatics studies, while the binding energy and interactions of chalcone epoxides with amino acid residues in each protein have been supported through molecular docking. The results of this study suggest that chalcone epoxide derivatives are promising anticancer drug candidates with potential for further development in the future.