Collect. Czech. Chem. Commun.
1999, 64, 217-228
https://doi.org/10.1135/cccc19990217
Antitumor Agents. 192. Antitubulin Effect and Cytotoxicity of C(7)-Oxygenated Allocolchicinoids
Jian Guana, Xiao-Kang Zhua, Arnold Brossia, Yoko Tachibanaa, Kenneth F. Bastowa, Pascal Verdier-Pinardb, Ernest Hamelb, Andrew T. McPhailc and Kuo-Hsiung Leea,*
a Natural Products Laboratory, Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599, U.S.A.
b Laboratory of Drug Discovery Research and Development, Development Therapeutics Program, Division of Cancer Treatment, Diagnosis and Centers, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, MD 21702, U.S.A.
c Paul M. Gross Chemical Laboratory, Duke University, Durham, NC 27708; U.S.A.
Abstract
Two allocolchicinoids 6 and 8, prepared from colchicine, together with allo compounds 9-11, made from 6 by reduction and regiodemethylation, were evaluated for antitubulin and antitumor activities. Structures of 6, 8, and 10 were confirmed by X-ray crystallographic analysis. Compounds 6, 8, and 9 have high tubulin binding affinity and display potent inhibitory activities against tubulin polymerization and solid human tumor cell lines. Particularly, drug-resistant KB cell lines, including KB-7d, KB-VCR, and KB-CPT, do not show marked resistance to these compounds.
Keywords: Colchicinoids; Colchicine; Allocolchicine; Antimitosis; Antitumor agents.
