Synthesis and Biological Evaluation of Novel Paclitaxel (Taxol) D-Ring Modified Analogues.
The semisynthesis and biological activity of paclitaxel (Taxol) analogues in which the oxygen atom in ring D is substituted by a sulfur or a selenium atom is presented. These derivatives were synthesized and tested in order to make more transparent the role of the oxetane ring in the biological activity of paclitaxel. The sulfur derivatives were found to be less active than paclitaxel in biological assays, while the selenium derivative could not be converted to its 4-acyl analogue. The results with the sulfur analogues suggest that the oxygen atom in the oxetane ring plays an important role in the mechanism by which paclitaxel exhibits its anticancer activity.
Gunatilaka
A. A. Leslie
AA
Laboratory of Drug Discovery Research and Development, Developmental Therapeutics Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland 21702.
Ramdayal
Frank D.
FD
Sarragiotto
Maria H.
MH
Kingston
David G. I.
DG
Sackett
Dan L.
DL
Hamel
Ernest
E