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
  • 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: [email protected].
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.