Design, Synthesis, and Mechanistic Studies of 5‐Substituted 2‐Oxindoles as Anticancer Agents

Key Points

• The research aims to design and synthesize oxindole derivatives as potential anticancer agents and assess their effectiveness and safety.
• Designed and synthesized 5-substituted 2-oxindoles with modifications at 1st and 3rd positions.
• Evaluated anticancer activity using the MTT assay across four cancer cell lines.
• Conducted toxicity assessments against noncancerous cell lines T293 and WI-38.
• Performed enzyme inhibition assays to identify EGFR and HER2 inhibition.
• Utilized molecular docking and MD simulations to analyze compound interactions with EGFR.
• MCF-7 cells showed the highest sensitivity to synthesized compounds, especially 4i, 4j, 4p, and 4q with IC50 < 40 µM.
• A549 cells demonstrated resistance, while MDA-MB-231 and HCT116 exhibited weak to moderate responses.
• Compounds 4i and 4p displayed favorable toxicity profiles, especially 4i with selectivity indices > 10.
• Compound 4i was identified as a potent EGFR inhibitor with an IC50 of 22.38 µM, outperforming 4p.
• Molecular docking revealed key interactions between compounds and EGFR, enhancing stability through additional bonding.