Synthesis and biological evaluation of fluorescently labeled epothilone analogs for tubulin binding studies

摘要

The two fluorescently labeled epothilones 14 and 15 have been synthesized using a modification of Nicolaou's macrolactonization and Stille coupling strategy. The cytotoxicities of the compounds were 6.1 and 2.7 mug/mL, respectively, against the A2870 ovarian cancer cell line, and 0.5 and 1.0 mug/mL, respectively, against the PC-3 prostate cancer cell line. The critical concentration of tubulin was 0.5 and 1.0 muM in the presence of 14 and 15, respectively, compared with 0.3 muM for paclitaxel. The fluorescent properties of the two molecules in solution and bound to microtubules are described. (C) 2003 Elsevier Ltd. All rights reserved. [References: 24]