title: Syntheses and biological evaluation of vinblastine congeners.
abstract: Sixty-two congeners of vinblastine (VLB), primarily with modifications of the piperidine ring in the carbomethoxycleavamine moiety of the binary alkaloid, were synthesized and evaluated for cytotoxicity against murine L1210 leukemia and RCC-2 rat colon cancer cells, and for their ability to inhibit polymerization of microtubular protein at < 10(-6) M, and for induction of spiralization of microtubular protein, and for microtubular disassembly at 10(-4) M concentrations. An ID50 range of >10(7) M concentrations was found for L1210 inhibition by these compounds, with the most active 1000x as potent as vinblastine.
authors.affiliation: Department of Chemistry, University of Vermont, Burlington, VT 05405, USA.
authors.forename: Martin E
authors.initials: ME
authors.lastname: Kuehne
authors.forename: William G
authors.initials: WG
authors.lastname: Bornmann
authors.forename: Istvan
authors.initials: I
authors.lastname: Markó
authors.forename: Yong
authors.initials: Y
authors.lastname: Qin
authors.forename: Karen L
authors.initials: KL
authors.lastname: LeBoulluec
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Frasier
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Tshilundu
authors.initials: T
authors.lastname: Mulamba
authors.forename: Carol L
authors.initials: CL
authors.lastname: Ensinger
authors.forename: Linda S
authors.initials: LS
authors.lastname: Borman
authors.forename: Anne E
authors.initials: AE
authors.lastname: Huot
authors.forename: Christopher
authors.initials: C
authors.lastname: Exon
authors.forename: Fred T
authors.initials: FT
authors.lastname: Bizzarro
authors.forename: Julia B
authors.initials: JB
authors.lastname: Cheung
authors.forename: Susan L
authors.initials: SL
authors.lastname: Bane
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy; D004354:Drug Screening Assays, Antitumor; D020128:Inhibitory Concentration 50; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008870:Microtubules / Q000737:chemistry / Q000187:drug effects; D051381:Rats; D013329:Structure-Activity Relationship; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014747:Vinblastine