Universidade do Grande Rio, Duque de Caxias, Brazil; Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco G, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia and Centro Nacional de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, Bloco G, Rio de Janeiro, Brazil; Instituto Nacional de Ciência e Tecnologia and Centro Nacional de Biologia Estrutural e Bioimagem, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Exp Parasitol. 2023 Jul;250:108549. doi: 10.1016/j.exppara.2023.108549. Epub 2023 May 16.
Trichomonas vaginalis is a protozoan that causes human trichomoniasis, a sexually transmitted infection (STI) that affects approximately 278 million people worldwide. The current treatment for human trichomoniasis is based on 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, known as Metronidazole (MTZ). Although effective in eliminating parasitic infection, MTZ is related to serious adverse effects and is not recommended during pregnancy. In addition, some strains are resistant to 5'-nitroimidazoles, prompting the development of alternative drugs for trichomoniasis. Here we show that SQ109 [N-adamantan-2-yl-N'-((E)-3,7-dimethyl-octa- 2,6-dienyl)-ethane-1,2-diamine], a drug under development (antitubercular drug candidate that completed Phase IIb/III) for the treatment of tuberculosis, and previously tested in Trypanosoma cruzi and Leishmania. SQ109 inhibited T.vaginalis growth with an IC50 of 3.15 μM. We used scanning and transmission electron microscopy to visualize the ultrastructural alterations induced by SQ109. The microscopy analysis showed morphological changes on the protozoan surface, where the cells became rounded with increasing surface projections. In addition, the hydrogenosomes increased their size and area occupied in the cell. Furthermore, the volume and a significant association of glycogen particles with the organelle were seen to be altered. A bioinformatics search was done about the compound to find its possible targets and mechanisms of action. Our observations identify SQ109 as a promising compound against T. vaginalis in vitro, suggesting its potential utility as an alternative chemotherapy for trichomoniasis.
阴道毛滴虫是一种原生动物，会引起人类滴虫病，这是一种性传播感染（STI），全球约有 2.78 亿人受到影响。目前治疗人类滴虫病的方法是基于 1-(2-羟乙基)-2-甲基-5-硝基咪唑，即甲硝唑（MTZ）。尽管 MTZ 能有效消除寄生虫感染，但它与严重的不良反应有关，不建议在怀孕期间使用。此外，一些菌株对 5'-硝基咪唑类药物具有耐药性，促使人们开发替代药物来治疗滴虫病。在这里，我们发现 SQ109[N-金刚烷-2-基-N'-((E)-3,7-二甲基-辛-2,6-二烯基)-乙烷-1,2-二胺]，这是一种正在开发中的药物（抗结核候选药物，已完成 IIb/III 期临床试验），用于治疗结核病，之前已在克氏锥虫和利什曼原虫中进行了测试。SQ109 抑制 T.vaginalis 生长的 IC50 为 3.15 μM。我们使用扫描和透射电子显微镜观察 SQ109 诱导的超微结构改变。显微镜分析显示，在原生动物表面上发生了形态变化，细胞变得圆形，表面突起增加。此外，氢体增大了其在细胞中的大小和所占面积。此外，还观察到体积和糖原颗粒与细胞器的显著关联发生改变。对该化合物进行了生物信息学搜索，以寻找其可能的靶标和作用机制。我们的观察结果表明，SQ109 是一种有前途的 T. vaginalis 体外化合物，表明其作为滴虫病替代化疗药物的潜在用途。
