Trichomonas vaginalis infects approximately 300 million people worldwide annually. Infected individuals have a higher susceptibility to more serious conditions such as cervical and prostate cancer. The parasite has developed increasing resistance to current drug therapies, with an estimated 5% of clinical cases resulting from resistant strains, creating the need for new therapeutic strategies with novel mechanisms of action. Nucleoside salvage pathway enzymes represent novel drug targets as these pathways are essential for the parasite's survival. The guanosine/adenosine/cytidine nucleoside hydrolase (GACNH) may be particularly important as its expression is upregulated under glucose‐limiting conditions mimicking those that occur during infection establishment. GACNH was screened against the NIH Clinical Collection to explore its druggability. Seven compounds were identified with IC₅₀ values <20 μM. Extensive overlap was found between inhibitors of GACNH and the adenosine/guanosine nucleoside hydrolase (AGNH), but no overlap was found with inhibitors of the uridine nucleoside hydrolase. The guanosine analog ribavirin was the only compound found to be specific for GACNH. Compounds that inhibit both AGNH and GACNH purine salvage pathway enzymes may prove critical given the role that GACNH appears to play in the early stages of infection.

中文翻译：

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阴道毛滴虫的鸟苷/腺苷/胞苷核苷水解酶的可药用性

阴道毛滴虫每年全世界大约感染3亿人。受感染的个体对更严重的疾病（例如宫颈癌和前列腺癌）的敏感性更高。该寄生虫对目前的药物疗法产生了越来越大的抗药性，估计有5％的临床病例是由抗药性菌株引起的，因此需要具有新作用机制的新治疗策略。核苷挽救途径酶代表了新型药物靶标，因为这些途径对于寄生虫的生存至关重要。鸟嘌呤/腺苷/胞苷核苷水解酶（GACNH）可能特别重要，因为它的表达在葡萄糖限制条件下（类似于在感染建立过程中发生的条件）被上调。针对NIH Clinical Collection对GACNH进行了筛选，以探索其可药用性。_50个值<20μM。在GACNH抑制剂和腺苷/鸟苷核苷水解酶（AGNH）的抑制剂之间发现了广泛的重叠，但与尿苷核苷水解酶的抑制剂没有发现重叠。鸟苷类似物利巴韦林是唯一发现对GACNH具有特异性的化合物。考虑到GACNH似乎在感染的早期阶段起着作用，抑制AGNH和GACNH嘌呤挽救途径酶的化合物可能被证明是至关重要的。