The influence of aromatic substitution at the 2-benzoyl moiety of paclitaxel on biological activity was investigated, following the Topliss Operational Scheme. Twelve paclitaxel derivatives were synthesized and evaluated in a microtubule assembly assay and for cytotoxicity against B16 melanoma cells. Most of the analogues were found to possess biological properties similar to paclitaxel.
Bibliographical noteFunding Information:
Financial support from the National Institutes of Health (CA 55141 and CA55100) is acknowledged. The Danish Research Academy ($930093) and Familien Hede Nielsens Fond are acknowledged for grants to Lise Falborg. Support is also acknowledged from the Scientific Education Partnership of Marion Merr¢ll Dow for a postdoctoral fellowship awarded to Thomas C. Boge and from the Kansas Health Foundation for a postdoctoral fellowship awarded to Syed M. AlL We arc grateful for the excellent technical assistance of Ms. Christine