SYNTHESIS AND BIOLOGICAL EVALUATION OF 2-ACYL ANALOGS OF PACLITAXEL (TAXOL)

The anticancer drug paclitaxel (Taxol) has been converted to a large n umber of 2-debenzoyl-2-aroyl derivatives by three different methods. T he bioactivities of the resulting analogues were determined in both tu bulin polymerization and cytotoxicity assays, and several analogues wi th enhanced activity as compared with paclitaxel were discovered. Corr elation of cytotoxicity in three cell lines with tubulin polymerizatio n activity showed reasonable agreement. Among the cell lines examined, the closest correlation with antitubulin activity was observed with a human ovarian carcinoma cell line.