Synthesis and biological evaluation of N-heterocyclic indolyl glyoxylamides as orally active anticancer agents

  • J Med Chem. 2003 Apr 24;46(9):1706-15. doi: 10.1021/jm020471r.
Wen-Tai Li  1 ,  Der-Ren Hwang ,  Ching-Ping Chen ,  Chien-Wei Shen ,  Chen-Long Huang ,  Tung-Wei Chen ,  Chi-Hung Lin ,  Yee-Ling Chang ,  Ying-Ying Chang ,  Yue-Kan Lo ,  Huan-Yi Tseng ,  Chu-Chung Lin ,  Jeng-Shin Song ,  Hua-Chien Chen ,  Shu-Jen Chen ,  Se-Hui Wu ,  Chiung-Tong Chen
Affiliations
  • 1. Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 9F, 161, Sec. 6, Min-Chiuan East Road, Nei-Hu, Taipei 114, Taiwan, ROC.
PMID: 12699388 DOI: 10.1021/jm020471r
Abstract

A series of N-heterocyclic indolyl glyoxylamides were synthesized and evaluated for in vitro and in vivo Anticancer activities. They exhibited a broad spectrum of Anticancer activity not only in murine leukemic Cancer cells but also in human gastric, breast, and uterus Cancer cells as well as their multidrug resistant sublines with a wide range of IC(50) values. They also induced Apoptosis and caused DNA fragmentation in human gastric Cancer cells. Among the compounds studied, 7 showed the most potent activity of growth inhibition (IC(50) = 17-1711 nM) in several human Cancer cells. Given orally, compounds 7 and 13 dose-dependently prolonged the survival of Animals inoculated with P388 leukemic Cancer cells. N-Heterocyclic indolyl glyoxylamides may be useful as orally active chemotherapeutic agents against Cancer and refractory cancerous diseases of multidrug resistance phenotype.