Synthesis, tubulin assembly, and antiproliferative activity against MCF7 and NCI/ADR-RES cancer cells of 10-O-acetyl-5'-hydroxybutitaxel.
A highly efficient kinetic resolution of racemic cis-4-(2-tert-butyldimethylsilyloxy-1,1-dimethyl)ethyl-3-tert-butyldimethylsilyloxy-azetidin-2-one with 7-O-triethylsilylbaccatin III was carried out to furnish 10-O-acetyl-5'-hydroxybutitaxel after removal of the silyl protecting groups. The compound was 50% as active as paclitaxel in a tubulin assembly assay and showed significantly decreased activity against MCF7 cell proliferation compared to paclitaxel.
Ge
Haibo
H
Department of Medicinal Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045, USA.
Wang
Jianmei
J
Kayser
Margaret M
MM
Himes
Richard H
RH
Georg
Gunda I
GI
D000818:Animals; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D015394:Molecular Structure; D017646:Organosilicon Compounds / Q000737:chemistry; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000187:drug effects* / Q000378:metabolism; D047090:beta-Lactams / Q000737:chemistry
C533913:10-O-acetyl-5'-hydroxybutitaxel; D017646:Organosilicon Compounds; D014404:Tubulin; D047090:beta-Lactams; D017239:Paclitaxel