Antitumor agents. Part 215: antitubulin effects of cytotoxic B-ring modified allocolchicinoids.
N-Acetylcolchinol methyl ether 1 served as the starting material to prepare the chloroacetamide (3) and epoxide (5) analogues. Both 3 and 5 were potent inhibitors of tubulin polymerization in vitro. Compound 3 was also 4-fold more cytotoxic than colchicine against the 1A9 tumor cell line and showed a unique cross-resistance profile.
Han
Shiqing
S
Natural Products Laboratory, School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599, USA.
Hamel
Ernest
E
Bastow
Kenneth F
KF
McPhail
Andrew T
AT
Brossi
Arnold
A
Lee
Kuo-Hsiung
KH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D003078:Colchicine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007202:Indicators and Reagents; D008958:Models, Molecular; D008968:Molecular Conformation; D014404:Tubulin / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007202:Indicators and Reagents; D014404:Tubulin; C032782:allocolchicine; D003078:Colchicine