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March 16, 2026ChemistrySelect0 citations

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

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MAMohd Farooque AhmedAAA.K. AggarwalRPRohit Pal

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.

Abstract

ABSTRACT In the present study, a series of oxindole‐based compounds modified at the 1 st and 3 rd positions were designed, synthesized, and structurally characterized using spectral techniques. Eighteen synthesized compounds were evaluated for anticancer activity against four cancer cell lines: A549, MCF‐7, MDA‐MB‐231, and HCT116 using the MTT assay. MCF‐7 showed the highest sensitivity, specially four compounds, namely, 4i , 4j , 4p , and 4q displayed significant activity (IC 50 10 against both cell lines. Enzyme inhibition assays demonstrated 4i as aEGFR (IC 50 = 22.38 µM) and HER2 (IC 50 = 44.86 µM) inhibitor, superior to 4p . In the molecular docking studies, four most active compounds ( 4i , 4j , 4p , and 4q ) revealed key polar interactions with Ser720, Thr790, and Thr854 of EGFR and fit into the hydrophobic pocket of EGFR; notably, 4i formed an additional π‐cation bond, enhancing stability. MD simulations of 4i ‐EGFR complex showed initial fluctuations (0–20 ns) followed by stabilization up to 60 ns.

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Cite This Study

Ahmed et al. (2026) studied this question.

synapsesocial.com/papers/69b79e638166e15b153ab995https://doi.org/10.1002/slct.202506619
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