Synthesis and screening of small molecule inhibitors of anthrax edema factor.
The synthesis and development of a novel class of molecules that inhibit anthrax edema factor, an adenylyl cyclase, is reported. These molecules are derived from the initial discovery that histidine and imidazole adducts of the prostaglandin PGE(2) reduce the net secretory response of cholera toxin-challenged mice and act directly on the action of anthrax edema factor, a calmodulin-dependent adenylyl cyclase. The simple enones examined in this letter were prepared by palladium-catalyzed Suzuki reaction.
Chemical Biology Program, Department of Pharmacology and Toxicology, The University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0650, USA.
Maria Estrella
ME
Jimenez
Kathryn
K
Bush
Jennifer
J
Pawlik
Laurie
L
Sower
Johnny W
JW
Peterson
Scott R
SR
Gilbertson
D000262:Adenylyl Cyclases / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D000881:Anthrax / Q000378:metabolism*; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000201:enzymology; D001427:Bacterial Toxins; D001665:Binding Sites; D002147:Calmodulin / Q000378:metabolism; D002384:Catalysis; D015232:Dinoprostone / Q000378:metabolism; D015195:Drug Design; D007659:Ketones; D051379:Mice; D008956:Models, Chemical; D010165:Palladium / Q000737:chemistry
D000890:Anti-Infective Agents; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D002147:Calmodulin; D007659:Ketones; C030325:anthrax toxin; D010165:Palladium; D000262:Adenylyl Cyclases; D015232:Dinoprostone