Trichomoniasis is the most common non-viral sexually transmitted infection, caused by the protozoan parasite Trichomonas vaginalis, affecting millions of people worldwide. The main treatment against trichomoniasis is metronidazole and other nitroimidazole derivatives, but up to twenty percent of clinical cases of trichomoniasis are resistant to these drugs. In this study, we used high-performance virtual screening to search for molecules that specifically bind to the protein, triosephosphate isomerase from T. vaginalis (TvTIM). By in silico molecular docking analysis, we selected six compounds from a chemical library of almost 500,000 compounds. While none of the six inhibited the enzymatic activity of recombinant triosephosphate isomerase isoforms, one compound (A4; 3,3′-{[4-(4-morpholinyl)phenyl]methylene}bis(4- hydroxy-2H-chromen-2-one) altered their fluorescence emission spectra, suggesting that this chemical might interfere in an important non-glycolytic function of TvTIM. In vitro assays demonstrate that A4 is not cytotoxic but does have trichomonacidal impact on T. vaginalis cultures.

With these results, we propose this compound as a potential drug with a new therapeutic target against Trichomonas vaginalis.

滴虫病是最常见的非病毒性性传播感染，由原生动物寄生虫阴道毛滴虫引起，影响全世界数百万人。滴虫病的主要治疗方法是甲硝唑和其他硝基咪唑衍生物，但高达 20% 的滴虫病临床病例对这些药物耐药。在这项研究中，我们使用高性能虚拟筛选来寻找与蛋白质特异性结合的分子，即来自阴道毛滴虫(TvTIM) 的磷酸丙糖异构酶。通过在 silico分子对接分析，我们从近 500,000 种化合物的化学库中选择了 6 种化合物。虽然这六种化合物都没有抑制重组磷酸丙糖异构酶异构体的酶活性，但一种化合物 (A4; 3,3'-{[4-(4-morpholinyl)phenyl]methylene}bis(4-hydroxy-2H-chromen-2-) a) 改变了它们的荧光发射光谱，表明这种化学物质可能会干扰 TvTIM 的一个重要的非糖酵解功能。体外试验表明 A4 没有细胞毒性，但对T.阴道培养物确实有滴虫酸影响。

有了这些结果，我们建议将该化合物作为一种潜在的药物，具有针对阴道毛滴虫的新治疗靶点。