Drug Design

Design, synthesis, antitumor evaluations and molecular modeling studies of novel 3,5-substituted indolin-2-one derivatives



To design and synthesize a novel class of antitumor agents, featuring the 3, 5-substituted indolin-2-one framework.


Based on enzyme binding features of (Z)-SU5402, introducing a β-pyrrole group at the 3-position of the indolin-2-one core, a series of novel 3,5-substituted indolin-2-ones were designed and synthesized. Four human carcinoma cell lines of A-431, A-549, MDA-MB-468, and Autosomal Dominant Polycystic Kidney disease were chosen for the cell proliferation assay.


Twenty new compounds (1a–t) with E configuration have been designed, synthesized and bioassayed. Their structural features were determined by nuclear magnetic resonance (NMR) spectra, low- and high-resolution mass spectra, and confirmed by X-ray crystallography. Although the enzyme assay showed a weak inhibition effect against the epidermal growth factor receptor, vascular endothelial growth factor receptor, fibroblast growth factor receptor and platelet-derived growth factor receptor tyrosine kinases, the cell-based antitumor activity was promising. Compounds 1g and 1h showed higher inhibitory activity toward the A-549 and MDA-MB-468 cell lines with IC50 of 0.065–9.4 umol/L.


This study provides a new template for further development of potent antitumor drugs.


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Corresponding authors

Correspondence to Hong Liu or Xiao-min Luo or Li-ping Lin.

Additional information

Project supported by the State Key Program of Basic Research of China (No 2002CB512802), the 863 Hi-Tech Program (No 2002AA233061 and 2003AA235011), the National Natural Science Foundation of China (No 20372069, 29725203 and 20472094).

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Li, Hh., Zhang, Xh., Tan, Jz. et al. Design, synthesis, antitumor evaluations and molecular modeling studies of novel 3,5-substituted indolin-2-one derivatives. Acta Pharmacol Sin 28, 140–152 (2007). https://doi.org/10.1111/j.1745-7254.2007.00473.x

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  • protein-tyrosine kinase
  • indolin-2-one
  • antitumor drug screening assays
  • drug design
  • molecular models

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