title: Synthesis and evaluation of [14C]-labelled and fluorescent-tagged paclitaxel derivatives as new biological probes.
abstract: Our present report deals with the preparation of hitherto unreported 7-([carbonyl-14C]-acetyl)paclitaxel 4 and two new bioactive 7-substituted fluorescent taxoids (FITC 9 and rhodamine 11), as well as evaluation towards their applications as biological probes. The results in this report demonstrate that (a) the new paclitaxel derivatives 4, 9, 11 could be prepared with good yields starting from paclitaxel; (b) the [14C]acetylation step was found to be better by using [14C]acetic anhydride rather than [14C]sodium acetate; (c) the radiochemical purity of 4 was 96% and its specific activity was 48 mCi/mmol; (d) the cytotoxicity of 4 was close to that of paclitaxel whereas 9, 11 were far less active than paclitaxel, but these cytotoxic levels were good enough for their biological applications; (e) the drug-quantitation by flow cytometric analysis using 9 and 11 was proved to be equally efficient with respect to the radioactivity-based determination employing 4; (f) the intracellular fluorescence mapping by 9 and 11 was found to be effective 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 11. Based on these results, the newly prepared paclitaxel derivatives can be considered as efficient biological probes and should find further use in relevant applications.
authors.affiliation: Department of Life Science, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
authors.forename: C S
authors.initials: CS
authors.lastname: Rao
authors.forename: J J
authors.initials: JJ
authors.lastname: Chu
authors.forename: R S
authors.initials: RS
authors.lastname: Liu
authors.forename: Y K
authors.initials: YK
authors.lastname: Lai
mesh_terms: D000107:Acetylation; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D001692:Biological Transport; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics*; D002289:Carcinoma, Non-Small-Cell Lung; D002453:Cell Cycle; D002470:Cell Survival / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate; D005456:Fluorescent Dyes / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007202:Indicators and Reagents; D007553:Isotope Labeling / Q000379:methods; D008175:Lung Neoplasms; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D017239:Paclitaxel / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity; D012235:Rhodamines; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002250:Carbon Radioisotopes; D005456:Fluorescent Dyes; D007202:Indicators and Reagents; D012235:Rhodamines; D016650:Fluorescein-5-isothiocyanate; D017239:Paclitaxel