Epothilone analogues with benzimidazole and quinoline side chains: chemical synthesis, antiproliferative activity, and interactions with tubulin
Publisher DOI
PubMed ID
19697384
Abstract
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.
Date Issued
2009
Publication Type
Article
Language(s)
en
Author(s)
Dietrich, Silvia Anthoine | |
Lindauer, Renate | |
Stierlin, Claire | |
Matesanz, Ruth | |
Notararigo, Sara | |
Díaz, José Fernando | |
Altmann, Karl-Heinz |
Additional Credits
Journal
Chemistry - a European journal
Publisher
Wiley-VCH
ISSN
0947-6539
Access(Rights)
metadata.only