title: Design, synthesis, and biochemical evaluation of novel cruzain inhibitors with potential application in the treatment of Chagas' disease.
abstract: A series of compounds bearing tetrahydronaphthalene, benzophenone, propiophenone, and related rigid molecular skeletons functionalized with thiosemicarbazone or unsaturated carbonyl moieties were prepared by chemical synthesis and evaluated for their ability to inhibit the enzyme cruzain. As potential treatment agents for Chagas' disease, three compounds from the group demonstrate potent inhibition of cruzain with IC(50) values of 17, 24, and 80 nM, respectively.
authors.affiliation: Baylor University, Department of Chemistry and Biochemistry and The Center for Drug Discovery, Waco, TX 76798, USA.
authors.forename: Rogelio
authors.initials: R
authors.lastname: Siles
authors.forename: Shen-En
authors.initials: SE
authors.lastname: Chen
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Pinney
authors.forename: Mary Lynn
authors.initials: ML
authors.lastname: Trawick
mesh_terms: D002244:Carbon / Q000737:chemistry; D014355:Chagas Disease / Q000188:drug therapy*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003546:Cysteine Endopeptidases; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors*; D012664:Semicarbazones / Q000737:chemistry*
chemical_list: D015800:Protozoan Proteins; D012664:Semicarbazones; D002244:Carbon; D003546:Cysteine Endopeptidases; C074032:cruzain, Trypanosoma cruzi