| Autor: |
Vargas Rigo G; Laboratório de Pesquisa em Parasitologia, Faculdade de Farmácia,Universidade Federal do Rio Grande do Sul,Av. Ipiranga, 2752, 90610-000, Porto Alegre, RS,Brazil., Petro-Silveira B; Laboratório de Pesquisa em Parasitologia, Faculdade de Farmácia,Universidade Federal do Rio Grande do Sul,Av. Ipiranga, 2752, 90610-000, Porto Alegre, RS,Brazil., Devereux M; The Inorganic Pharmaceutical and Biomimetic Research Centre, Focas Research Institute,Dublin Institute of Technology,Dublin,Ireland., McCann M; Chemistry Department,Maynooth University, National University of Ireland,Maynooth,Ireland., Souza Dos Santos AL; Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes, Departamento de Microbiologia Paulo de Góes,Universidade Federal do Rio de Janeiro,Rio de Janeiro, RJ,Brazil., Tasca T; Laboratório de Pesquisa em Parasitologia, Faculdade de Farmácia,Universidade Federal do Rio Grande do Sul,Av. Ipiranga, 2752, 90610-000, Porto Alegre, RS,Brazil. |
| Abstrakt: |
Trichomonas vaginalis is responsible for the most common non-viral, sexually transmitted infection, human trichomoniasis, and is associated with an increased susceptibility to HIV. An escalation in resistance (2.5-10%) to the clinical drug, metronidazole (MTZ), has been detected and this compound also has adverse side-effects. Therefore, new treatment options are urgently required. Herein, we investigate the possible anti-T. vaginalis activity of 1,10-phenanthroline-5,6-dione (phendione) and its metal complexes, [Ag(phendione)2]ClO4 and [Cu(phendione)3](ClO4)2·4H2O. Minimum inhibitory concentration (MIC) against T. vaginalis ATCC 30236 and three fresh clinical isolates and mammalian cells were performed using serial dilution generating IC50 and CC50 values. Drugs combinations with MTZ were evaluated by chequerboard assay. A strong anti-T. vaginalis activity was found for all test compounds. IC50 values obtained for [Cu(phendione)3](ClO4)2·4H2O were similar or lower than those obtained for MTZ. In vitro assays with normal cells showed low cytotoxicity and [Cu(phendione)3](ClO4)2·4H2O presented a high selectivity index (SI) for fibroblasts (SI = 11.39) and erythrocytes (SI > 57.47). Chequerboard assay demonstrated that the combination of [Cu(phendione)3](ClO4)2·4H2O with MTZ leads to synergistic interaction, which suggests distinct mechanisms of action of the copper-phendione complex and avoiding the MTZ resistance pathways. Our results highlight the importance of phendione-based drugs as potential molecules of pharmaceutical interest. |
