title: In vivo and in vitro antimalarial activity of 4-nerolidylcatechol.
abstract: 4-Nerolidylcatechol (4-NC) isolated from Piper peltatum L. (Piperaceae) was evaluated for in vitro antiplasmodial activity against Plasmodium falciparum (cultures of both standard CQR (K1) and CQS (3D7) strains and two Amazonian field isolates) and for in vivo antimalarial activity using the Plasmodium berghei-murine model. 4-NC exhibits significant in vitro and moderate in vivo antiplasmodial activity. 4-NC administered orally and subcutaneously at doses of 200, 400 and 600 mg/kg/day suppressed the growth of P. berghei by up to 63% after four daily treatments (days 1-4). Also, 4-NC exhibited important in vitro antiplasmodial activity against both standard and field P. falciparum strains in which 50% inhibition of parasite growth (IC(50) ) was produced at concentrations of 0.05-2.11 μg/mL and depended upon the parasite strain. Interestingly, healthy (non-infected) mice that received 4-NC orally presented (denatured) blood plasma which exhibited significant in vitro activity against P. falciparum. This is evidence that mouse metabolism allows 4-NC or active metabolites to enter the blood. Further chemical and pharmacological studies are necessary to confirm the potential of 4-NC as a new antimalarial prototype.
authors.affiliation: Laboratório da Gerência de Malária, Fundação de Medicina Tropical do Amazonas, Manaus, AM, Brazil.
authors.forename: Luiz Francisco
authors.initials: LF
authors.lastname: Rocha E Silva
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Silva Pinto
authors.forename: Adrian Martin
authors.initials: AM
authors.lastname: Pohlit
authors.forename: Etienne Louis Jacques
authors.initials: EL
authors.lastname: Quignard
authors.forename: Pedro Paulo Ribeiro
authors.initials: PP
authors.lastname: Vieira
authors.forename: Wanderli Pedro
authors.initials: WP
authors.lastname: Tadei
authors.forename: Francisco Célio Maia
authors.initials: FC
authors.lastname: Chaves
authors.forename: Jean Francisco
authors.initials: JF
authors.lastname: Samonek
authors.forename: Carlos Alberto Jatoba
authors.initials: CA
authors.lastname: Lima
authors.forename: Mônica Regina Farias
authors.initials: MR
authors.lastname: Costa
authors.forename: Maria das Graças Costa
authors.initials: Md
authors.lastname: Alecrim
authors.forename: Valter Ferreira
authors.initials: VF
authors.lastname: Andrade-Neto
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D001938:Brazil; D002396:Catechols / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D008288:Malaria / Q000097:blood / Q000188:drug therapy* / Q000469:parasitology; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy / Q000469:parasitology; D051379:Mice; D031701:Piper / Q000737:chemistry*; D010962:Plasmodium berghei / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*
chemical_list: C110583:4-nerolidylcatechol; D000962:Antimalarials; D002396:Catechols