Aim: To design and synthesize a novel class of antitumor agents, featuring the 3,
5-substituted indolin-2-one framework. Methods: Based on enzyme binding features
of (Z)-SU5402, introducing a -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. Results: Twenty new compounds (1aCt) 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 0.065C9.4 mol/L.
Conclusion: This study provides a new template for further development of
potent antitumor drugs.