Tubulysin analogs incorporating desmethyl and dimethyl tubuphenylalanine derivatives.
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 IC(50) values similar to combretastatin A4 and the hemiasterlin analog HTI-286.
Balasubramanian
Ranganathan
R
Department of Medicinal Chemistry, 308 Harvard Street S.E., 8-101 Weaver-Densford Hall, University of Minnesota, Minneapolis, MN 55455-0353, USA.
Raghavan
Bhooma
B
Steele
Jaeson C
JC
Sackett
Dan L
DL
Fecik
Robert A
RA
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D009842:Oligopeptides / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000473:pathology*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D013267:Stilbenes / Q000494:pharmacology; D013329:Structure-Activity Relationship; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000494:pharmacology*
D000970:Antineoplastic Agents; C473896:HTI-286; D009842:Oligopeptides; D013267:Stilbenes; D050257:Tubulin Modulators; D010649:Phenylalanine; C467070:hemiasterlin; C058728:fosbretabulin