title: Antimalarial activity of 4-(5-trifluoromethyl-1H-pyrazol-1-yl)-chloroquine analogues.
abstract: The antimalarial activity of chloroquine-pyrazole analogues, synthesized from the reaction of 1,1,1-trifluoro-4-methoxy-3-alken-2-ones with 4-hydrazino-7-chloroquinoline, has been evaluated in vitro against a chloroquine resistant Plasmodium falciparum clone. Parasite growth in the presence of the test drugs was measured by incorporation of [(3)H]hypoxanthine in comparison to controls with no drugs. All but one of the eight (4,5-dihydropyrazol-1-yl) chloroquine 2 derivatives tested showed a significant activity in vitro, thus, are a promising new class of antimalarials. The three most active ones were also tested in vivo against Plasmodium berghei in mice. However, the (pyrazol-1-yl) chloroquine 3 derivatives were mostly inactive, suggesting that the aromatic functionality of the pyrazole ring was critical.
authors.affiliation: Centro de Pesquisas René Rachou, Fiocruz e Departamento de Parasitologia-Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil.
authors.forename: Wilson
authors.initials: W
authors.lastname: Cunico
authors.forename: Cleber A
authors.initials: CA
authors.lastname: Cechinel
authors.forename: Helio G
authors.initials: HG
authors.lastname: Bonacorso
authors.forename: Marcos A P
authors.initials: MA
authors.lastname: Martins
authors.forename: Nilo
authors.initials: N
authors.lastname: Zanatta
authors.forename: Marcus V N
authors.initials: MV
authors.lastname: de Souza
authors.forename: Isabela O
authors.initials: IO
authors.lastname: Freitas
authors.forename: Rodrigo P P
authors.initials: RP
authors.lastname: Soares
authors.forename: Antoniana U
authors.initials: AU
authors.lastname: Krettli
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology* / Q000627:therapeutic use; D002738:Chloroquine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008288:Malaria / Q000188:drug therapy*; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C508946:4-(5-trifluoromethyl-1H-pyrazol-1-yl)-chloroquine; D000962:Antimalarials; D011720:Pyrazoles; C031280:pyrazole; D002738:Chloroquine