Design, Synthesis, Biological Evaluation, and Molecular Docking of Heterocyclic Aromatic Thioether Derivatives Containing Amides

Abstract Aromatic heterocyclic sulfides are an essential class of organic compounds and synthetic intermediates, with broad applications in fields such as medicine, agriculture, dyes, and materials science. Importantly, the combination of heterocycles through amide and thioether bonds can effectively enhance their biological activity by leveraging synergistic effects. In this study, we synthesized a series of heterocyclic aromatic sulfide derivatives containing amide groups by incorporating bromoacetic acid and benzylamine into thiol‐containing heterocycles or thiophene derivatives. This synthesis was carried out under conditions that ensure high atom economy and environmental friendliness. Subsequently, their antiproliferative effects were evaluated using the MTT assay, which demonstrated selective inhibition of human cervical cancer (HeLa) cells with no significant toxicity to LO2 cells. Notably, compound 3f reduced HeLa cell viability to 63.67% and exhibited good solubility. Molecular docking studies further revealed that compound 3f showed strong interactions with the EGFR receptor, highlighting its potential as a promising anticancer agent.