A series of tubulysin analogs in which one of the stereogenic centers of tubuphenylalanine was eliminated were synthesized. All compounds were tested for antiproliferative activity towards ovarian cancer cells and for inhibition of tubulin polymerization. The dimethyl analogs were generally more active than the desmethyl analogs, and four analogs have tubulin polymerization IC50 values similar to combretastatin A4 and the hemiasterlin analog HTI-286.
Bibliographical noteFunding Information:
This work was generously supported by the American Cancer Society, Grant RSG-05-105-01-CDD (to R.A.F.), and was supported in part by intramural funds from the National Institute of Child Health and Human Development, NIH. Funding for NMR instrumentation in the Department of Biochemistry, Molecular Biology, and Biophysics was provided by the University of Minnesota Medical School, NSF (BIR-961477), and the Minnesota Medical Foundation.
Copyright 2008 Elsevier B.V., All rights reserved.
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