2. Academic Validation
  3. Synthesis and antimalarial activity of quinones and structurally-related oxirane derivatives

Synthesis and antimalarial activity of quinones and structurally-related oxirane derivatives

  • Eur J Med Chem. 2016 Jan 27:108:134-140. doi: 10.1016/j.ejmech.2015.11.020.
Paula F Carneiro 1,  Maria C R F Pinto 1,  Roberta K F Marra 2,  Fernando de C da Silva 2,  Jackson A L C Resende 3,  Luiz F Rocha E Silva 4,  Hilkem G Alves 5,  Gleyce S Barbosa 5,  Marne C de Vasconcellos 5,  Emerson S Lima 5,  Adrian M Pohlit 4,  Vitor F Ferreira 6
Affiliations

Affiliations

  • 1 Universidade Federal do Rio de Janeiro, Instituto de Pesquisas de Produtos Naturais, 21944-970 Rio de Janeiro, RJ, Brazil.
  • 2 Universidade Federal Fluminense, Instituto de Química, Departamento de Química Orgânica, 24020-150 Niterói, RJ, Brazil.
  • 3 Universidade Federal Fluminense, Instituto de Química, Departamento de Química Inorgânica, 24020-150 Niterói, RJ, Brazil.
  • 4 Instituto Nacional de Pesquisas da Amazônia, Laboratório de Princípios Ativos da Amazônia, Av. André Araújo, 2936 Manaus, Brazil.
  • 5 Universidade Federal do Amazonas, Faculdade de Ciências Farmacêuticas, 69010-300 Manaus, AM, Brazil.
  • 6 Universidade Federal Fluminense, Instituto de Química, Departamento de Química Orgânica, 24020-150 Niterói, RJ, Brazil. Electronic address: cegvito@vm.uff.br.
PMID: 26638044 DOI: 10.1016/j.ejmech.2015.11.020
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.

Keywords

Epoxides; Infectious disease; Lapachone; Malaria; Naphthoquinones.

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