title: Synthesis, in vitro, and in vivo evaluation of phosphate ester derivatives of combretastatin A-4.
abstract: Combretastatin A-4 disodiumphosphate (CA4P), a prodrug formulation of the natural product combretastatin A-4 (CA4), is currently in clinical investigation for the treatment of cancer. In vivo, CA4P is rapidly enzymatically converted to CA4, a potent inhibitor of tubulin polymerization (IC(50)=1-2 microM), and rapidly causes bloodflow shutdown in tumor tissues. A variety of alkyl and aryl di- and triesters of CA4P have been synthesized and evaluated as potential CA4 prodrugs and/or stable CA4P analogues.
authors.affiliation: Department of Chemistry & Biochemistry, Center for Drug Discovery, Baylor University, Waco, TX 76798-7348, USA.
authors.forename: Mallinath B
authors.initials: MB
authors.lastname: Hadimani
authors.forename: Jianyi
authors.initials: J
authors.lastname: Hua
authors.forename: M Devan
authors.initials: MD
authors.lastname: Jonklaas
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Kessler
authors.forename: Yezhou
authors.initials: Y
authors.lastname: Sheng
authors.forename: Adrian
authors.initials: A
authors.lastname: Olivares
authors.forename: Rajendra P
authors.initials: RP
authors.lastname: Tanpure
authors.forename: Aimee
authors.initials: A
authors.lastname: Weiser
authors.forename: Jianxing
authors.initials: J
authors.lastname: Zhang
authors.forename: Klaus
authors.initials: K
authors.lastname: Edvardsen
authors.forename: Robert R
authors.initials: RR
authors.lastname: Kane
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Pinney
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D010755:Organophosphates / Q000138:chemical synthesis* / Q000494:pharmacology; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology; D013267:Stilbenes / Q000737:chemistry* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D010755:Organophosphates; D011355:Prodrugs; D013267:Stilbenes; C058728:fosbretabulin