title: Synthesis and antimalarial activity of sulfonamide chalcone derivatives.
abstract: A series of sulfonamide chalcone derivatives were synthesized and investigated for their abilities to inhibit beta-hematin formation in vitro and their activity against cultured Plasmodium falciparum parasites. Inhibition of beta-hematin formation was minimal in the aromatic ring of the chalcone moiety as it appeared for compounds 4b, 4d-f, and greatest with compounds 4g (IC50 0.48 microM) and 4k (IC50 0.50 microM) with a substitution of 3,4,5-trimethoxyl and 3-pyridinyl, respectively. In this study, the most active compound resulted 1[4'-N(2'',5''-dichlorophenyl) sulfonyl-amidephenyl]-3-(4-methylphenyl)-2-propen-1-one 4i, effective as antimalarial by the inhibition of cultured P. falciparum parasites (1 microM). These studies open up the novel possibility of development of sulfonamide derivatives as antimalarials that target beta-hematin formation and the inhibition of the development of cultured P. falciparum parasites, which should help delay the rapid onset of resistance to drugs acting at only a single site. Results with these assays suggest that chalcones exert their antimalarial activity via multiple mechanisms.
authors.affiliation: Laboratorio de Síntesis Orgánica, Universidad Central de Venezuela, Caracas, Venezuela. jdomingu@cantv.net
authors.forename: José N
authors.initials: JN
authors.lastname: Domínguez
authors.forename: Caritza
authors.initials: C
authors.lastname: León
authors.forename: Juan
authors.initials: J
authors.lastname: Rodrigues
authors.forename: Neira
authors.initials: N
authors.lastname: Gamboa de Domínguez
authors.forename: Jiri
authors.initials: J
authors.lastname: Gut
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Rosenthal
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002599:Chalcone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D006420:Hemeproteins / Q000037:antagonists & inhibitors; D020128:Inhibitory Concentration 50; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D006420:Hemeproteins; D013449:Sulfonamides; C020753:hemozoin; D002599:Chalcone