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Updated: Jul 18, 2026
Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Design, synthesis, antitumor evaluations and molecular modeling studies of novel 3,5-substituted indolin-2-one
Hai-Hong Li1, Xiu-Hua Zheng, Jin-Zhi Tan
1Center for Drug Discovery and Design, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 201203, China.
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 beta-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 1 g and 1 h showed higher inhibitory activity toward the A-549 and MDA-MB-468 cell lines with IC(50 ) of 0.065-9.4 micromol/L.
Conclusion:
This study provides a new template for further development of potent antitumor drugs.
