大环紫杉醇双内酯的合成及其生物活性

Syntheses and bioactivities of macrocyclic paclitaxel bis-lactones.

作者信息

Liu Changhui, Schilling Jennifer K, Ravindra Rudravajhala, Bane Susan, Kingston David G I

机构信息

Department of Chemistry, M/C 0212, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA.

出版信息

Bioorg Med Chem. 2004 Dec 1;12(23):6147-61. doi: 10.1016/j.bmc.2004.09.002.

DOI:10.1016/j.bmc.2004.09.002

PMID:15519159

Abstract

Five macrocyclic paclitaxel bis-lactones and their corresponding open chain taxoids were synthesized as models of the tubulin-binding conformation of paclitaxel. Macrocyclic lactones with a 19-21-membered ring underwent isomerization to form smaller rings. The lactones were evaluated for cytotoxicity and tubulin-polymerization ability. All five macrocyclic paclitaxel lactones were active, but less so than paclitaxel, while the rearranged macrocyclic lactones and the corresponding open-chain taxoids were much less active or inactive.

摘要

合成了五种大环紫杉醇双内酯及其相应的开链紫杉烷类化合物，作为紫杉醇微管蛋白结合构象的模型。具有19至21元环的大环内酯发生异构化形成较小的环。对这些内酯进行了细胞毒性和微管蛋白聚合能力评估。所有五种大环紫杉醇内酯均具有活性，但活性低于紫杉醇，而重排的大环内酯和相应的开链紫杉烷类化合物活性则低得多或无活性。