Druggability of the guanosine/adenosine/cytidine nucleoside hydrolase from Trichomonas vaginalis
Druggability of the guanosine/adenosine/cytidine nucleoside hydrolase from Trichomonas vaginalis
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DOI：
10.1111/cbdd.13341
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发表时间：
2018-10-01
影响因子：
3
通讯作者：
Stockman, Brian J.
中科院分区：
文献类型：
--
作者：
Alam, Rayyan;Barbarovich, Allen T.;Stockman, Brian J.
阴道毛滴虫每年感染全球约3亿人。受感染的个体更容易患上更严重的疾病，如宫颈癌和前列腺癌。寄生虫对目前的药物治疗产生了越来越大的耐药性，估计有5%的临床病例是由耐药菌株引起的，这就需要具有新作用机制的新治疗策略。核苷补救途径酶代表了新的药物靶标，因为这些途径对于寄生虫的生存至关重要。鸟苷/腺苷/胞苷核苷水解酶（GACNH）可能特别重要，因为其表达在葡萄糖限制条件下上调，模拟感染建立期间发生的情况。GACNH针对NIH临床收集进行筛选以探索其可药用性。鉴定了7个化合物的IC 50值
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