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  • Title: 2-amino and 2'-aminocombretastatin derivatives as potent antimitotic agents.
    Author: Chang JY, Yang MF, Chang CY, Chen CM, Kuo CC, Liou JP.
    Journal: J Med Chem; 2006 Oct 19; 49(21):6412-5. PubMed ID: 17034147.
    Abstract:
    A novel series of 2-amino and 2'-aminocombretastatin derivatives were synthesized and evaluated for antitumor activity. Several compounds had excellent antiproliferative activity as inhibitors of tubulin polymerization. Compounds 11, 20, and 21 with IC(50) values of 1.6, 1.7, and 1.8 microM, respectively, exhibited more potent inhibition of tubulin polymerization than colchicine and approximately as active as combretastatin A-4. They also displayed antiproliferative activity with an IC(50) values ranging from 11 to 44 nM in a variety of human cell lines from different organs. Structure activity relationship information suggests that the NH(2) substituent at the 2-position of either ring A or ring B in combretastatin molecular skeleton may play an important role in the bioactivity of this series of compounds.
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