Laboratório de Pesquisa em Parasitologia, Faculdade de Farmácia,Universidade Federal do Rio Grande do Sul,Av. Ipiranga, 2752, 90610-000, Porto Alegre, RS,Brazil.
The Inorganic Pharmaceutical and Biomimetic Research Centre, Focas Research Institute,Dublin Institute of Technology,Dublin,Ireland.
Parasitology. 2019 Aug;146(9):1179-1183. doi: 10.1017/S003118201800152X. Epub 2018 Sep 12.
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)32·4H2O. 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)32·4H2O were similar or lower than those obtained for MTZ. In vitro assays with normal cells showed low cytotoxicity and Cu(phendione)32·4H2O 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)32·4H2O 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.
阴道毛滴虫是引起最常见的非病毒性性传播感染——人类滴虫病的原因，并且与 HIV 易感性增加有关。已经检测到对临床药物甲硝唑（MTZ）的耐药性（2.5-10%）上升，并且该化合物也具有不良的副作用。因此，迫切需要新的治疗选择。在此，我们研究了 1,10-菲啰啉-5,6-二酮（菲酮）及其金属配合物[Ag（菲酮）2]ClO4和[Cu（菲酮）3]（ClO4）2·4H2O对阴道毛滴虫 ATCC 30236和三个新鲜临床分离株及哺乳动物细胞的潜在抗滴虫活性。采用连续稀释法生成 IC50 和 CC50 值，对 T. vaginalis ATCC 30236 和三个新鲜临床分离株及哺乳动物细胞进行最低抑菌浓度（MIC）测定。用棋盘试验评估与 MTZ 的药物组合。所有测试化合物均表现出很强的抗阴道毛滴虫活性。[Cu（菲酮）3]（ClO4）2·4H2O 的 IC50 值与 MTZ 获得的值相似或更低。对正常细胞的体外试验显示低细胞毒性，[Cu（菲酮）3]（ClO4）2·4H2O 对成纤维细胞（SI = 11.39）和红细胞（SI > 57.47）具有高选择性指数（SI）。棋盘试验表明，[Cu（菲酮）3]（ClO4）2·4H2O 与 MTZ 的组合导致协同相互作用，这表明铜菲酮配合物的作用机制不同，避免了 MTZ 的耐药途径。我们的研究结果强调了基于菲酮的药物作为潜在的药物感兴趣的分子的重要性。
