2. Academic Validation
  3. Novel methyl indolinone-6-carboxylates containing an indole moiety as angiokinase inhibitors

Novel methyl indolinone-6-carboxylates containing an indole moiety as angiokinase inhibitors

  • Eur J Med Chem. 2017 Oct 20:139:492-502. doi: 10.1016/j.ejmech.2017.08.031.
Mingze Qin 1,  Ye Tian 1,  Xiaoqing Sun 1,  Simiao Yu 1,  Juanjuan Xia 1,  Ping Gong 1,  Haotian Zhang 2,  Yanfang Zhao 3
Affiliations

Affiliations

  • 1 Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenyang 110016, PR China.
  • 2 Department of Pharmacology, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address: zhanghaotian2087@163.com.
  • 3 Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry of Education, 103 Wenhua Road, Shenyang 110016, PR China. Electronic address: yanfangzhao@126.com.
PMID: 28826084 DOI: 10.1016/j.ejmech.2017.08.031
Abstract

A novel series of methyl indolinone-6-carboxylates bearing an indole moiety were identified as potent angiokinase inhibitors. The most active compound, A8, potently targeted the kinase activities of vascular endothelial growth factor receptors 2 and 3, and platelet-derived growth factor receptors α and β, with IC50 values in the nanomolar range. In addition, A8 effectively suppressed the proliferation of human umbilical vein endothelial cells, and HT-29 and MCF-7 Cancer cells, by inducing Apoptosis. Compound A8 is thus a promising candidate for further investigation.

Keywords

Angiokinase inhibitors; Antitumour activity; Methyl indolinone-6-carboxylates; Ring-fused strategy.

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