Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5970-5977 |
| Number of pages | 8 |
| Journal | European Journal of Medicinal Chemistry |
| Volume | 46 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 2011 |
| Externally published | Yes |
Bibliographical note
Funding Information:We thank the National Natural Sciences Foundation of China (No. 81072516, 20802066 ) and National Science & Technology Major Project “Key New Drug Creation and Manufacturing Program” of China (No. 2009ZX09501-010 ) for the financial support.
Keywords
- 2-Indolinones
- Antitumor agent
- Apoptosis
- VEGFR-2
