title: Combretastatin dinitrogen-substituted stilbene analogues as tubulin-binding and vascular-disrupting agents.
abstract: Several stilbenoid compounds having structural similarity to the combretastatin group of natural products and characterized by the incorporation of two nitrogen-bearing groups (amine, nitro, serinamide) have been prepared by chemical synthesis and evaluated in terms of biochemical and biological activity. The 2',3'-diamino B-ring analogue 17 demonstrated remarkable cytotoxicity against selected human cancer cell lines in vitro (average GI 50 = 13.9 nM) and also showed good activity in regard to inhibition of tubulin assembly (IC 50 = 2.8 microM). In addition, a single dose (10 mg/kg) of compound 17 caused a 40% tumor-selective blood flow shutdown in tumor-bearing SCID mice at 24 h, thus suggesting the potential value of this compound and its corresponding salt formulations as new vascular-disrupting agents.
authors.affiliation: Department of Chemistry and Biochemistry, Baylor University, Waco, TX 76798-7348, USA.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Siles
authors.forename: J Freeland
authors.initials: JF
authors.lastname: Ackley
authors.forename: Mallinath B
authors.initials: MB
authors.lastname: Hadimani
authors.forename: John J
authors.initials: JJ
authors.lastname: Hall
authors.forename: Benon E
authors.initials: BE
authors.lastname: Mugabe
authors.forename: Rajsekhar
authors.initials: R
authors.lastname: Guddneppanavar
authors.forename: Keith A
authors.initials: KA
authors.lastname: Monk
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Chapuis
authors.forename: George R
authors.initials: GR
authors.lastname: Pettit
authors.forename: David J
authors.initials: DJ
authors.lastname: Chaplin
authors.forename: Klaus
authors.initials: K
authors.lastname: Edvardsen
authors.forename: Mary Lynn
authors.initials: ML
authors.lastname: Trawick
authors.forename: Charles M
authors.initials: CM
authors.lastname: Garner
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Pinney
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001632:Bibenzyls / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007941:Leukemia P388; D051379:Mice; D015394:Molecular Structure; D009369:Neoplasms / Q000098:blood supply; D012039:Regional Blood Flow / Q000187:drug effects; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014404:Tubulin / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D001632:Bibenzyls; D013267:Stilbenes; D014404:Tubulin; C040105:combretastatin