Synthesis and evaluation of [C-14]-labelled and fluorescent-tagged paclitaxel derivatives as new biological probes

Our present report deals with the preparation of hitherto unreported 7-([ca rbonyl-C-14]-acetyl)paclitaxel 4 and two new bioactive 7-substituted fluore scent taxoids (FITC 9 and rhodamine 11), as well as evaluation towards thei r applications as biological probes. The results in this report demonstrate that (a) the new paclitaxel derivatives 4, 9, 11 could be prepared with go od yields starting from paclitaxel; (b) the [C-14]acetylation step was foun d to be better by using [C-14]acetic anhydride rather than [C-14]sodium ace tate; (c) the radiochemical purity of 4 was 96% and its specific activity w as 48 mCi/mmol; (d) the cytotoxicity of 4 was close to that of paclitaxel w hereas 9, 11 were far less active than paclitaxel, but these cytotoxic leve ls were good enough for their biological applications; (e) the drug-quantit ation by flow cytometric analysis using 9 and 11 was proved to be equally e fficient with respect to the radioactivity-based determination employing 4; (f) the intracellular fluorescence mapping by 9 and 11 was found to be eff ective and the microtubule network pattern was visible in both the cases; ( g) the overall fluorescence imaging efficiency was better with 11 while the intensity of fluorescence was higher with 9; (h) staining of nucleolus was observed in fluorescence studies of both 9 and II. Based on these results; the newly prepared paclitaxel derivatives can be considered as efficient b iological probes and should find further use in relevant applications. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.