Scaffold-hopping strategy: Synthesis and biological evaluation of 5,6-fused bicyclic heteroaromatics to identify orally bioavailable anticancer agents

Yen Shih Tung, Mohane Selvaraj Coumar, Yu Shan Wu, Hui Yi Shiao, Jang Yang Chang, Jing Ping Liou, Paritosh Shukla, Chun Wei Chang, Chi Yen Chang, Ching Chuan Kuo, Teng Kuang Yeh, Chin Yu Lin, Jian Sung Wu, Su Ying Wu, Chun Chen Liao, Hsing Pang Hsieh

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Utilizing scaffold-hopping drug-design strategy, we sought to identify a backup drug candidate for BPR0L075 (1), an indole-based anticancer agent. For this purpose, 5,6-fused bicyclic heteroaromatic scaffolds were designed and synthesized through shuffling of the nitrogen from the N-1 position or by insertion of one or two nitrogen atoms into the indole core of 1. Among these, 7-azaindole core 12 showed potent in vitro anticancer activity and improved oral bioavailability (F = 35%) compared with 1 (F <10%).

Original languageEnglish
Pages (from-to)3076-3080
Number of pages5
JournalJournal of Medicinal Chemistry
Volume54
Issue number8
DOIs
Publication statusPublished - Apr 28 2011

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Antineoplastic Agents
Nitrogen
Drug Design
Biological Availability
Pharmaceutical Preparations
indole
6-methoxy-3-(3',4',5'-trimethoxybenzoyl)-1H-indole
In Vitro Techniques
7-azaindole dimer

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

Cite this

Scaffold-hopping strategy : Synthesis and biological evaluation of 5,6-fused bicyclic heteroaromatics to identify orally bioavailable anticancer agents. / Tung, Yen Shih; Coumar, Mohane Selvaraj; Wu, Yu Shan; Shiao, Hui Yi; Chang, Jang Yang; Liou, Jing Ping; Shukla, Paritosh; Chang, Chun Wei; Chang, Chi Yen; Kuo, Ching Chuan; Yeh, Teng Kuang; Lin, Chin Yu; Wu, Jian Sung; Wu, Su Ying; Liao, Chun Chen; Hsieh, Hsing Pang.

In: Journal of Medicinal Chemistry, Vol. 54, No. 8, 28.04.2011, p. 3076-3080.

Research output: Contribution to journalArticle

Tung, YS, Coumar, MS, Wu, YS, Shiao, HY, Chang, JY, Liou, JP, Shukla, P, Chang, CW, Chang, CY, Kuo, CC, Yeh, TK, Lin, CY, Wu, JS, Wu, SY, Liao, CC & Hsieh, HP 2011, 'Scaffold-hopping strategy: Synthesis and biological evaluation of 5,6-fused bicyclic heteroaromatics to identify orally bioavailable anticancer agents', Journal of Medicinal Chemistry, vol. 54, no. 8, pp. 3076-3080. https://doi.org/10.1021/jm101027s
Tung, Yen Shih ; Coumar, Mohane Selvaraj ; Wu, Yu Shan ; Shiao, Hui Yi ; Chang, Jang Yang ; Liou, Jing Ping ; Shukla, Paritosh ; Chang, Chun Wei ; Chang, Chi Yen ; Kuo, Ching Chuan ; Yeh, Teng Kuang ; Lin, Chin Yu ; Wu, Jian Sung ; Wu, Su Ying ; Liao, Chun Chen ; Hsieh, Hsing Pang. / Scaffold-hopping strategy : Synthesis and biological evaluation of 5,6-fused bicyclic heteroaromatics to identify orally bioavailable anticancer agents. In: Journal of Medicinal Chemistry. 2011 ; Vol. 54, No. 8. pp. 3076-3080.
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