Abstract:
:Structure-activity analyses of synthetic disorazole C(1) and eight of its analogs indicate that the presence of a vinyl oxirane moiety or a tetraene sequence is not necessary for potent cytotoxic and antimitotic properties. Using an automated multiparameter fluorescence-based cellular assay to simultaneously probe the effects of disorazole analogs on cellular microtubules, mitotic arrest, and cytotoxicity, we found that disorazole C(1) enhanced the mitotic index and chromatin condensation and arrested cells in the G2/M phase of the cell cycle. All structural analogs and synthesis precursors of disorazole C(1) were at least two orders of magnitude less potent than the parent compound, thus indicating that both the functional group array and the three-dimensional conformation of the parent compound are critical for interaction with the biological target. We conclude that disorazole C(1) is a potent inducer of mitotic arrest and hypothesize that this biological activity may be mediated by microtubule perturbation.
journal_name
Chem Biol Drug Desjournal_title
Chemical biology & drug designauthors
Wipf P,Graham TH,Vogt A,Sikorski RP,Ducruet AP,Lazo JSdoi
10.1111/j.1747-0285.2005.00313.xkeywords:
subject
Has Abstractpub_date
2006-01-01 00:00:00pages
66-73issue
1eissn
1747-0277issn
1747-0285pii
JPP313journal_volume
67pub_type
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