title: Synthesis and evaluation of 3-aroylindoles as anticancer agents: metabolite approach.
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.
authors: Division of Biotechnology and Pharmaceutical Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 350, Taiwan, Republic of China.
authors: Yu-Shan
authors: YS
authors: Wu
authors: Mohane Selvaraj
authors: MS
authors: Coumar
authors: Jang-Yang
authors: JY
authors: Chang
authors: Hsu-Yi
authors: HY
authors: Sun
authors: Fu-Ming
authors: FM
authors: Kuo
authors: Ching-Chuan
authors: CC
authors: Kuo
authors: Ying-Jun
authors: YJ
authors: Chen
authors: Chi-Yen
authors: CY
authors: Chang
authors: Chia-Ling
authors: CL
authors: Hsiao
authors: Jing-Ping
authors: JP
authors: Liou
authors: Ching-Ping
authors: CP
authors: Chen
authors: Hsien-Tsung
authors: HT
authors: Yao
authors: Yi-Kun
authors: YK
authors: Chiang
authors: Uan-Kang
authors: UK
authors: Tan
authors: Chiung-Tong
authors: CT
authors: Chen
authors: Chang-Ying
authors: CY
authors: Chu
authors: Su-Ying
authors: SY
authors: Wu
authors: Teng-Kuang
authors: TK
authors: Yeh
authors: Chin-Yu
authors: CY
authors: Lin
authors: Hsing-Pang
authors: HP
authors: Hsieh
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D003078:Colchicine / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D051379:Mice; D051381:Rats; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: C488735:6-methoxy-3-(3',4',5'-trimethoxybenzoyl)-1H-indole; D000970:Antineoplastic Agents; D007211:Indoles; D050257:Tubulin Modulators; D003078:Colchicine