Anti-Trichomonas vaginalis activity of 1,10-phenanthroline-5,6-dione-based metallodrugs and synergistic effect with metronidazole
| Autor: | Brenda Petro-Silveira, Graziela Vargas Rigo, André L.S. Santos, Tiana Tasca, Malachy McCann, Michael Devereux |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Erythrocytes Serial dilution 030106 microbiology Microbial Sensitivity Tests Biology medicine.disease_cause Cell Line 03 medical and health sciences Minimum inhibitory concentration Inhibitory Concentration 50 Mice Metronidazole medicine Trichomonas vaginalis Animals Humans Cytotoxicity IC50 Trichomoniasis In vitro toxicology Drug Synergism Fibroblasts medicine.disease Molecular biology 030104 developmental biology Infectious Diseases Animal Science and Zoology Parasitology Female Trichomonas Vaginitis medicine.drug Phenanthrolines |
| Zdroj: | Parasitology. 146(9) |
| ISSN: | 1469-8161 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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