title: Effects of C7 substitutions in a high affinity microtubule-binding taxane on antitumor activity and drug transport.
abstract: Some C-7 modified analogs of 3, a taxane with high affinity for binding to microtubules, were prepared through multistep transformations. Most of the analogs, bearing less lipophilic C-7 substituents than propionyl in 3, exhibited comparable binding affinities to microtubules but less cytotoxicity against drug-sensitive as well as multidrug-resistant tumor cells overexpressing P-glycoprotein. In addition, these C7 modifications increased P-glycoprotein-mediated drug transport in both directions in a Caco-2 cell assay.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Xiao
authors.forename: Ju
authors.initials: J
authors.lastname: Wu
authors.forename: Chiara
authors.initials: C
authors.lastname: Trigili
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.forename: Joseph W K
authors.initials: JW
authors.lastname: Chu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhao
authors.forename: Peihua
authors.initials: P
authors.lastname: Lu
authors.forename: Li
authors.initials: L
authors.lastname: Sheng
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Frances J
authors.initials: FJ
authors.lastname: Sharom
authors.forename: Isabel
authors.initials: I
authors.lastname: Barasoain
authors.forename: J Fernando
authors.initials: JF
authors.lastname: Diaz
authors.forename: Wei-shuo
authors.initials: WS
authors.lastname: Fang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D001952:Bridged-Ring Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008870:Microtubules / Q000737:chemistry*; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane