Synthesis and biological evaluation of 2-indolinone derivatives as potential antitumor agents
- Eur J Med Chem. 2011 Dec;46(12):5970-7. doi: 10.1016/j.ejmech.2011.10.009.
- 1. College of Pharmaceutical Sciences, Zhejiang University, 388 Yuhangtang Road, Hangzhou 310058, PR China.
Three series of 3-substituted-indolin-2-ones and azaindolin-2-ones have been synthesized and showed potential antiproliferative activity to Cancer cell lines. The inhibition activities on VEGF-induced VEGFR phosphorylation were observed for selected 2-indolinones. Among the compounds synthesized, 5-fluoroindolin-2-one derivative 23 with a pyridone unit showed the most significant enzymatic and cellular activities. Flow cytometric analysis indicates that 23 plays a role in suppressing HCT-116 cell proliferation via G1 phase arrest and Apoptosis in a dose dependent manner. The binding mode of compound 23 complexed with VEGFR-2 was predicted using FlexX algorithm. Described here are the chemistry and biological testing for these series which will guide the design and optimization of novel 2-indolione antitumor agents.