2. Academic Validation
  3. Synthesis and evaluation of 3-aroylindoles as anticancer agents: metabolite approach

Synthesis and evaluation of 3-aroylindoles as anticancer agents: metabolite approach

  • J Med Chem. 2009 Aug 13;52(15):4941-5. doi: 10.1021/jm900060s.
Yu-Shan Wu 1,  Mohane Selvaraj Coumar,  Jang-Yang Chang,  Hsu-Yi Sun,  Fu-Ming Kuo,  Ching-Chuan Kuo,  Ying-Jun Chen,  Chi-Yen Chang,  Chia-Ling Hsiao,  Jing-Ping Liou,  Ching-Ping Chen,  Hsien-Tsung Yao,  Yi-Kun Chiang,  Uan-Kang Tan,  Chiung-Tong Chen,  Chang-Ying Chu,  Su-Ying Wu,  Teng-Kuang Yeh,  Chin-Yu Lin,  Hsing-Pang Hsieh
Affiliations

Affiliation

  • 1 Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 350, Taiwan, Republic of China.
PMID: 19586033 DOI: 10.1021/jm900060s
Abstract

BPR0L075 (2) is a potential Anticancer drug candidate designed from Combretastatin A-4 (1) based on the bioisosterism principle. Metabolites of 2, proposed from in vitro human microsome studies, were synthesized, leading to the identification of metabolite-derived analogue 10 with 40-350 pM potency against various Cancer cell lines. Insights gained from the major inactive metabolite of 2 led to the development of 29, with better pharmacokinetics and improved potency in the tumor xenograft model than 2.

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