Antitumor agents. Part 186:11For part 185, see ref. [1]. Synthesis and biological evaluation of demethylcolchiceinamide analogues as cytotoxic DNA topoisomerase II inhibitors
作者:Jian Guan、Xiao-Kang Zhu、Yoko Tachibana、Kenneth F. Bastow、Arnold Brossi、Ernest Hamel、Kuo-Hsiung Lee
DOI:10.1016/s0968-0896(98)00165-5
日期:1998.11
Demethylation of colchiceinamide (2) and its analogues (3-10) afforded a novel class of mammalian DNA topoisomerase II inhibitors (2a-10a) without displaying tubulin inhibitory activity. All target compounds inhibited the catalytic activity of topoisomerase II at drug concentrations at 100 microM. An in vitro cytotoxicity assay indicated that compounds 3a and 8a were strong and tissue-selective cytotoxic
Synthesis and biological evaluation of various colchicine analogues through the mixed-lymphocyte reaction (MLR), lymphoproliferation, and inhibitory effects on the inflammatory genes are described. In addition, a new series of immunosuppressive agents developed on the structural basis of colchicine, as well as their structure-activity relationships is reported. The most potent analogue 20a exhibited an excellent immunosuppressive activity on in vivo skin-allograft model, which is comparable to that of cyclosporin A. (C) 2009 Elsevier Ltd. All rights reserved.
Rapoport et al., Journal of the American Chemical Society, 1954, vol. 76, p. 3693,3697