Synthesis, biological activity and tubulin binding poses of 1-deoxy-9-(R)-dihydrotaxane analogs.
1-Deoxy-9alpha-dihydrotaxane analogs 9 and 10 were semi-synthesized from 1-deoxybaccatin VI, isolated from Taxus mairei, and tested for cytotoxic activity. Taxane 9 is 10-fold less cytotoxic than paclitaxel, while 10 is equally active. In the tubulin polymerization assay (ED(50) values), 10 is 4-fold less effective than paclitaxel, but 3-fold superior to 9. These observations can be explained by analysis of the corresponding taxane/beta-tubulin complexes.
Yuan
Tian-Hai
TH
Department of Chemistry, Shanghai University, Shanghai 200444, China.
Jiang
Yi
Y
Wang
Xiao-Hong
XH
Wang
Dian-Long
DL
Bannerjee
Abhijit
A
Bane
Susan
S
Snyder
James P
JP
Lin
Hai-Xia
HX
D001952:Bridged-Ring Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry; D013237:Stereoisomerism; D043823:Taxoids / Q000138:chemical synthesis / Q000494:pharmacology; D020946:Taxus / Q000737:chemistry; D014404:Tubulin / Q000187:drug effects*; D050257:Tubulin Modulators / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
C538854:1-deoxybaccatin VI; D001952:Bridged-Ring Compounds; D043823:Taxoids; D014404:Tubulin; D050257:Tubulin Modulators; C080625:taxane