Synthesis, in vitro, and in vivo evaluation of phosphate ester derivatives of combretastatin A-4.
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.
Hadimani
Mallinath B
MB
Department of Chemistry & Biochemistry, Center for Drug Discovery, Baylor University, Waco, TX 76798-7348, USA.
Hua
Jianyi
J
Jonklaas
M Devan
MD
Kessler
Raymond J
RJ
Sheng
Yezhou
Y
Olivares
Adrian
A
Tanpure
Rajendra P
RP
Weiser
Aimee
A
Zhang
Jianxing
J
Edvardsen
Klaus
K
Kane
Robert R
RR
Pinney
Kevin G
KG
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
D020533:Angiogenesis Inhibitors; D010755:Organophosphates; D011355:Prodrugs; D013267:Stilbenes; C058728:fosbretabulin