STRUCTURE MODIFICATIONS AND THEIR INFLUENCES ON ANTITUMOR AND OTHER RELATED ACTIVITIES OF TAXOL AND ITS ANALOGS - Medicinal Chemistry of Bioactive Natural Products - page 73

STRUCTURE MODIFICATIONS AND
THEIR INFLUENCES ON ANTITUMOR
AND OTHER RELATED ACTIVITIES
OF TAXOL AND ITS ANALOGS
W EI -S HUO F ANG ,Q I -C HENG F ANG , AND X IAO -T IAN L IANG
Institute of Materia Medica, Chinese Academy of Medical Sciences, Beijing, P. R. China
3.1 DISCOVERY AND RESEARCH AND DEVELOPMENT
OF TAXOL
Taxol 1a is an antitumor plant diterpene isolated from the yew tree Taxus spp. in the
late 1960s. It was named taxol at the time of its first isolation by Wani et al. 1 In the
1990s, when Bristol-Myers Squibb (BMS) launched it on the market, Taxol was
registered as an anticancer product, and Taxol was assigned a generic name, pacli-
taxel. Both taxol and paclitaxel are referred to in this chapter to describe the same
compound.
The discovery of Taxol is a fruit of a National Cancer Institute (NCI)-sponsored
project on identification of antitumor agents from natural resources. Bioassay-
guided fractionation led to the isolation of this unique compound from Taxus bre-
vifolia (pacific yew). Wani et al. also identified another famous antitumor natural
product camptothecin. Unlike camptothecin, which was abandoned in the phase
of clinical trial because of its severe toxicity, Taxol was almost discarded at the pre-
liminary phase because it only exhibited moderate in vitro activity toward P388, a
murine leukemia cell line that was used in the standard evaluation system by NCI
researchers at that time. However, it was rescued by a subsequent finding of its
strong and selective antitumor activities toward several solid tumors, and more