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 act...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2008-05, Vol.18 (9), p.2996-2999
Main Authors: Balasubramanian, Ranganathan, Raghavan, Bhooma, Steele, Jaeson C., Sackett, Dan L., Fecik, Robert A.
Format: Article
Language:English
Subjects:
Animals
Anticancer agents
Antineoplastic agents
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - pharmacology
Biological and medical sciences
Cell Line, Tumor
Cell Proliferation - drug effects
Cytotoxicity
Female
General aspects
Humans
Inhibitory Concentration 50
Medical sciences
Models, Chemical
Natural products
Oligopeptides - pharmacology
Ovarian Neoplasms - pathology
Pharmacology. Drug treatments
Phenylalanine - analogs & derivatives
Phenylalanine - chemical synthesis
Phenylalanine - pharmacology
Stilbenes - pharmacology
Structure-Activity Relationship
Tubulin
Tubulin Modulators - chemical synthesis
Tubulin Modulators - pharmacology
Tubulysin
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Summary: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.
ISSN:0960-894X
0968-0896
1464-3405
1464-3391
DOI:10.1016/j.bmcl.2008.03.046