Synthesis and structure-activity relationships of 3-aminobenzophenones as antimitotic agents

Jing Ping Liou, Jang Yang Chang, Chun Wei Chang, Chi Yen Chang, Neeraj Mahindroo, Fu Ming Kuo, Hsing Pang Hsieh

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Abstract

A new series of 3-aminobenzophenone compounds as potent inhibitors of tubulin polymerization was discovered based on the mimic of the aminocombretastatin molecular skeleton. Lead compounds 5 and 11, with alkoxy groups at the C-4 position of B-ring, were potent cytotoxic agents and inhibitors of tubulin polymerization through the binding to the colchicine-binding site of tubulin. The corresponding antitubulin activities of 5 and 11 were similar to or greater than combretastatin A-4 and AVE-8063. Replacement of the methoxy group with a chloro group in the B ring of aminobenzopheneones (3, 8, and 9) caused drastic decrease in cytotoxic and antitubulin activity except in compounds 4 and 10, which could result from a unique alignment between chloro and amino groups located at the para position to each other. SAR information revealed that introduction of an amino group at the C-3 position in B ring of benzophenones, in addition to a methoxy group at the C-4 position, plays an important role for maximal cytotoxicity.

Original languageEnglish
Pages (from-to)2897-2905
Number of pages9
JournalJournal of Medicinal Chemistry
Volume47
Issue number11
DOIs
Publication statusPublished - May 20 2004
Externally publishedYes

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Tubulin Modulators
Antimitotic Agents
Structure-Activity Relationship
Benzophenones
Lead compounds
Cytotoxins
Colchicine
Tubulin
Cytotoxicity
Skeleton
Binding Sites

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Liou, J. P., Chang, J. Y., Chang, C. W., Chang, C. Y., Mahindroo, N., Kuo, F. M., & Hsieh, H. P. (2004). Synthesis and structure-activity relationships of 3-aminobenzophenones as antimitotic agents. Journal of Medicinal Chemistry, 47(11), 2897-2905. https://doi.org/10.1021/jm0305974

Synthesis and structure-activity relationships of 3-aminobenzophenones as antimitotic agents. / Liou, Jing Ping; Chang, Jang Yang; Chang, Chun Wei; Chang, Chi Yen; Mahindroo, Neeraj; Kuo, Fu Ming; Hsieh, Hsing Pang.

In: Journal of Medicinal Chemistry, Vol. 47, No. 11, 20.05.2004, p. 2897-2905.

Research output: Contribution to journalArticle

Liou, JP, Chang, JY, Chang, CW, Chang, CY, Mahindroo, N, Kuo, FM & Hsieh, HP 2004, 'Synthesis and structure-activity relationships of 3-aminobenzophenones as antimitotic agents', Journal of Medicinal Chemistry, vol. 47, no. 11, pp. 2897-2905. https://doi.org/10.1021/jm0305974
Liou, Jing Ping ; Chang, Jang Yang ; Chang, Chun Wei ; Chang, Chi Yen ; Mahindroo, Neeraj ; Kuo, Fu Ming ; Hsieh, Hsing Pang. / Synthesis and structure-activity relationships of 3-aminobenzophenones as antimitotic agents. In: Journal of Medicinal Chemistry. 2004 ; Vol. 47, No. 11. pp. 2897-2905.
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