Affiliation: | aDepartamento de Química Orgânica, Instituto de Química, UFF, 24020-150 Niterói, RJ, Brazil bInstituto de Química, Universidade de Brasília, 70910-970 Brasília, DF, Brazil cLaboratório de Biologia Celular, Instituto Oswaldo Cruz, FIOCRUZ, 21045-900 Rio de Janeiro, RJ, Brazil dNúcleo de Pesquisas em Produtos Naturais, UFRJ, 21944-971 Rio de Janeiro, RJ, Brazil eInstituto de Química e Biotecnologia, UFAL, Tabuleiro do Martins, 57072-970 Maceió, Alagoas, Brazil |
Abstract: | New naphthoquinone derivatives were synthesized and assayed against bloodstream trypomastigote forms of Trypanosoma cruzi, the etiological agent of Chagas’ disease. The compounds were rationalized based on hybrid drugs and appear as important compounds against this parasite. From nor-lapachol were prepared five substituted ortho-naphthofuranquinones, a non-substituted para-naphthofuranquinone, a new oxyrane and an azide and from -lapachone a new non-substituted para-naphthofuranquinone. Other five substituted ortho-naphthofuranquinones recently designed as cytotoxic, were also evaluated. The most active compounds were the ortho naphthofuranquinones 3-(4-methoxyphenylamino)-2,3-dihydro-2,2-dimethylnaphtho[1,2-b]furan-4,5-dione and 3-(3-nitrophenylamino)-2,3-dihydro-2,2-dimethylnaphtho[1,2-b]furan-4,5-dione with trypanocidal activity higher than that of benznidazole, the standard drug. The compounds were rationalized based on hybrid drugs and appear as important compounds against T. cruzi. The trypanocidal activity of these substances endowed with redox properties representing a good starting point for a medicinal chemistry program aiming the chemotherapy of Chagas’ disease. |