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

Yu Shan Wu; 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

doi:10.1021/jm900060s

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

Yu Shan Wu
, 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

Research output: Contribution to journal › Article › peer-review

97 Citations (Scopus)

Abstract

BPR0L075 (2) is a potential anticancer drug candidate designed from Combretastatin A-4 (1) based on the bioisosterismprinciple.Metabolites of 2, proposed from in vitrohumanmicrosome 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.

Original language	English
Pages (from-to)	4941-4945
Number of pages	5
Journal	Journal of Medicinal Chemistry
Volume	52
Issue number	15
DOIs	https://doi.org/10.1021/jm900060s
Publication status	Published - Aug 13 2009

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Molecular Medicine
Drug Discovery

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10.1021/jm900060s

Cite this

Wu, Y. S., Coumar, M. S., Chang, J. Y., Sun, H. Y., Kuo, F. M., Kuo, C. C., Chen, Y. J., Chang, C. Y., Hsiao, C. L., Liou, J. P., Chen, C. P., Yao, H. T., Chiang, Y. K., Tan, U. K., Chen, C. T., Chu, C. Y., Wu, S. Y., Yeh, T. K., Lin, C. Y., & Hsieh, H. P. (2009). Synthesis and evaluation of 3-aroylindoles as anticancer agents: Metabolite approach. Journal of Medicinal Chemistry, 52(15), 4941-4945. https://doi.org/10.1021/jm900060s

Wu, YS, Coumar, MS, Chang, JY, Sun, HY, Kuo, FM, Kuo, CC, Chen, YJ, Chang, CY, Hsiao, CL, Liou, JP, Chen, CP, Yao, HT, Chiang, YK, Tan, UK, Chen, CT, Chu, CY, Wu, SY, Yeh, TK, Lin, CY & Hsieh, HP 2009, 'Synthesis and evaluation of 3-aroylindoles as anticancer agents: Metabolite approach', Journal of Medicinal Chemistry, vol. 52, no. 15, pp. 4941-4945. https://doi.org/10.1021/jm900060s

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abstract = "BPR0L075 (2) is a potential anticancer drug candidate designed from Combretastatin A-4 (1) based on the bioisosterismprinciple.Metabolites of 2, proposed from in vitrohumanmicrosome 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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AU - Kuo, Fu Ming

AU - Kuo, Ching Chuan

AU - Chen, Ying Jun

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AU - Hsiao, Chia Ling

AU - Liou, Jing Ping

AU - Chen, Ching Ping

AU - Yao, Hsien Tsung

AU - Chiang, Yi Kun

AU - Tan, Uan Kang

AU - Chen, Chiung Tong

AU - Chu, Chang Ying

AU - Wu, Su Ying

AU - Yeh, Teng Kuang

AU - Lin, Chin Yu

AU - Hsieh, Hsing Pang

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

Abstract

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ASJC Scopus subject areas

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