title: Synthesis and biological evaluation of 2-acyl analogues of paclitaxel (Taxol).
abstract: The anticancer drug paclitaxel (Taxol) has been converted to a large number of 2-debenzoyl-2-aroyl derivatives by three different methods. The bioactivities of the resulting analogues were determined in both tubulin polymerization and cytotoxicity assays, and several analogues with enhanced activity as compared with paclitaxel were discovered. Correlation of cytotoxicity in three cell lines with tubulin polymerization activity showed reasonable agreement. Among the cell lines examined, the closest correlation with antitubulin activity was observed with a human ovarian carcinoma cell line.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, New Jersey 05843, USA.
authors.forename: D G
authors.initials: DG
authors.lastname: Kingston
authors.forename: A G
authors.initials: AG
authors.lastname: Chaudhary
authors.forename: M D
authors.initials: MD
authors.lastname: Chordia
authors.forename: M
authors.initials: M
authors.lastname: Gharpure
authors.forename: A A
authors.initials: AA
authors.lastname: Gunatilaka
authors.forename: P I
authors.initials: PI
authors.lastname: Higgs
authors.forename: J M
authors.initials: JM
authors.lastname: Rimoldi
authors.forename: L
authors.initials: L
authors.lastname: Samala
authors.forename: P G
authors.initials: PG
authors.lastname: Jagtap
authors.forename: P
authors.initials: P
authors.lastname: Giannakakou
authors.forename: Y Q
authors.initials: YQ
authors.lastname: Jiang
authors.forename: C M
authors.initials: CM
authors.lastname: Lin
authors.forename: E
authors.initials: E
authors.lastname: Hamel
authors.forename: B H
authors.initials: BH
authors.lastname: Long
authors.forename: C R
authors.initials: CR
authors.lastname: Fairchild
authors.forename: K A
authors.initials: KA
authors.lastname: Johnston
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001704:Biopolymers; D002384:Catalysis; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001704:Biopolymers; D014404:Tubulin; D011092:Polyethylene Glycols; D017239:Paclitaxel