Epothilone analogues with benzimidazole and quinoline side chains: chemical synthesis, antiproliferative activity, and interactions with tubulin

Dietrich, Silvia Anthoine; Lindauer, Renate; Stierlin, Claire; Gertsch, Jürg; Matesanz, Ruth; Notararigo, Sara; Díaz, José Fernando; Altmann, Karl-Heinz (2009). Epothilone analogues with benzimidazole and quinoline side chains: chemical synthesis, antiproliferative activity, and interactions with tubulin. Chemistry - a European journal, 15(39), pp. 10144-57. Weinheim: Wiley-VCH 10.1002/chem.200901376

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A series of epothilone B and D analogues bearing isomeric quinoline or functionalized benzimidazole side chains has been prepared by chemical synthesis in a highly convergent manner. All analogues have been found to interact with the tubulin/microtubule system and to inhibit human cancer cell proliferation in vitro, albeit with different potencies (IC(50) values between 1 and 150 nM). The affinity of quinoline-based epothilone B and D analogues for stabilized microtubules clearly depends on the position of the N-atom in the quinoline system, while the induction of tubulin polymerization in vitro appears to be less sensitive to N-positioning. The potent inhibition of human cancer cell growth by epothilone analogues bearing functionalized benzimidazole side chains suggests that these systems might be conjugated with tumor-targeting moieties to form tumor-targeted prodrugs.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine
UniBE Contributor:	Gertsch, Jürg
ISSN:	0947-6539
Publisher:	Wiley-VCH
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:12
Last Modified:	05 Dec 2022 14:22
Publisher DOI:	10.1002/chem.200901376
PubMed ID:	19697384
Web of Science ID:	000270854200025
URI:	https://boris.unibe.ch/id/eprint/31618 (FactScience: 196249)