title: Synthesis and evaluation of new antimalarial phenylurenyl chalcone derivatives.
abstract: Phenylurenyl chalcone derivatives have been synthesized and tested as inhibitors of in vitro development of a chloroquine-resistant strain of Plasmodium falciparum, activity of the cysteine protease falcipain-2, in vitro globin hydrolysis, beta-hematin formation, and murine Plasmodium berghei malaria. The most active antimalarial compound was 1-[3'-N-(N'-phenylurenyl)phenyl]-3(3,4,5-trimethoxyphenyl)-2-propen-1-one 49, with an IC(50) of 1.76 microM for inhibition of P. falciparum development. Results suggest that chalcones exert their antimalarial activity via multiple mechanisms.
authors.affiliation: Laboratorio de Síntesis Orgánica, Facultad de Farmacia, 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; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003546:Cysteine Endopeptidases / Q000737:chemistry; D005914:Globins / Q000378:metabolism; D006418:Heme / Q000737:chemistry; D006420:Hemeproteins / Q000138:chemical synthesis; D006868:Hydrolysis; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D010671:Phenylurea Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects; D011108:Polymers; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D047188:Chalcones; D006420:Hemeproteins; D010671:Phenylurea Compounds; D011108:Polymers; D011480:Protease Inhibitors; C020753:hemozoin; D006418:Heme; D005914:Globins; D003546:Cysteine Endopeptidases; C416224:falcipain 2