title: Synthesis and antimalarial activity of quinones and structurally-related oxirane derivatives.
abstract: A series of eighteen quinones and structurally-related oxiranes were synthesized and evaluated for in vitro inhibitory activity against the chloroquine-sensitive 3D7 clone of the human malaria parasite Plasmodium falciparum. 2-amino and 2-allyloxynaphthoquinones exhibited important antiplasmodial activity (median inhibitory concentrations (IC50) < 10 μM). Oxiranes 6 and 25, prepared respectively by reaction of α-lapachone and tetrachloro-p-quinone with diazomethane in a mixture of ether and ethanol, exhibited the highest antiplasmodial activity and low cytotoxicity against human fibroblasts (MCR-5 cell line). The active compounds could represent a good prototype for an antimalarial lead molecule.
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Pesquisas de Produtos Naturais, 21944-970 Rio de Janeiro, RJ, Brazil.
authors.forename: Paula F
authors.initials: PF
authors.lastname: Carneiro
authors.affiliation: Universidade Federal do Rio de Janeiro, Instituto de Pesquisas de Produtos Naturais, 21944-970 Rio de Janeiro, RJ, Brazil.
authors.forename: Maria C R F
authors.initials: MCRF
authors.lastname: Pinto
authors.affiliation: Universidade Federal Fluminense, Instituto de Química, Departamento de Química Orgânica, 24020-150 Niterói, RJ, Brazil.
authors.forename: Roberta K F
authors.initials: RKF
authors.lastname: Marra
authors.affiliation: Universidade Federal Fluminense, Instituto de Química, Departamento de Química Orgânica, 24020-150 Niterói, RJ, Brazil.
authors.forename: Fernando de C
authors.initials: FC
authors.lastname: da Silva
authors.affiliation: Universidade Federal Fluminense, Instituto de Química, Departamento de Química Inorgânica, 24020-150 Niterói, RJ, Brazil.
authors.forename: Jackson A L C
authors.initials: JALC
authors.lastname: Resende
authors.affiliation: Instituto Nacional de Pesquisas da Amazônia, Laboratório de Princípios Ativos da Amazônia, Av. André Araújo, 2936 Manaus, Brazil.
authors.forename: Luiz F
authors.initials: LF
authors.lastname: Rocha E Silva
authors.affiliation: Universidade Federal do Amazonas, Faculdade de Ciências Farmacêuticas, 69010-300 Manaus, AM, Brazil.
authors.forename: Hilkem G
authors.initials: HG
authors.lastname: Alves
authors.affiliation: Universidade Federal do Amazonas, Faculdade de Ciências Farmacêuticas, 69010-300 Manaus, AM, Brazil.
authors.forename: Gleyce S
authors.initials: GS
authors.lastname: Barbosa
authors.affiliation: Universidade Federal do Amazonas, Faculdade de Ciências Farmacêuticas, 69010-300 Manaus, AM, Brazil.
authors.forename: Marne C
authors.initials: MC
authors.lastname: de Vasconcellos
authors.affiliation: Universidade Federal do Amazonas, Faculdade de Ciências Farmacêuticas, 69010-300 Manaus, AM, Brazil.
authors.forename: Emerson S
authors.initials: ES
authors.lastname: Lima
authors.affiliation: Instituto Nacional de Pesquisas da Amazônia, Laboratório de Princípios Ativos da Amazônia, Av. André Araújo, 2936 Manaus, Brazil.
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Pohlit
authors.affiliation: Universidade Federal Fluminense, Instituto de Química, Departamento de Química Orgânica, 24020-150 Niterói, RJ, Brazil. Electronic address: cegvito@vm.uff.br.
authors.forename: Vitor F
authors.initials: VF
authors.lastname: Ferreira
mesh_terms: D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005027:Ethylene Oxide / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects*; D011809:Quinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000962:Antimalarials; D011809:Quinones; D005027:Ethylene Oxide
keywords: Epoxides; Infectious disease; Lapachone; Malaria; Naphthoquinones