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

The two fluorescently labeled epothilones and have been synthesized using a modification of Nicolaouʹs macrolactonization and Stille coupling strategy. The cytotoxicities of the compounds were 6.1 and 2.7 μg/mL, respectively, against the A2870 ovarian cancer cell line, and 0.5 and 1.0 μg/mL, respectively, against the PC-3 prostate cancer cell line. The critical concentration of tubulin was 0.5 and 1.0 μM in the presence of and , respectively, compared with 0.3 μM for paclitaxel. The fluorescent properties of the two molecules in solution and bound to microtubules are described.