@article{APS3818,
author = {Hai-hong Li and Xiu-hua Zhang and Jin-zhi Tan and Li-li Chen and Hong Liu and Xiao-min Luo and Xu Shen and Li-ping Lin and Kai-xian Chen and Jian Ding and Hua-liang Jiang},
title = {Design, synthesis, antitumor evaluations and molecular modeling studies of novel 3,5-substituted indolin-2-one derivatives},
journal = {Acta Pharmacologica Sinica},
volume = {28},
number = {1},
year = {2016},
keywords = {},
abstract = {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 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. Results: 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 μmol/L.
Conclusion: This study provides a new template for further development of
potent antitumor drugs.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/3818}
}