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General Review Article

靶向Kinetoplastid和Apicomplexan胸苷生物合成作为一种抗原虫策略

卷 26, 期 22, 2019

页: [4262 - 4279] 页: 18

弟呕挨: 10.2174/0929867325666180926154329

价格: $65

摘要

动囊体和apicomplexan寄生虫包括负责人类疾病的原生动物群，对人类健康和发展中国家的社会经济增长产生了严重影响。化学疗法是控制这些病原生物的主要选择，核苷酸代谢被认为是提供抗菌治疗靶标的有希望的领域。胸苷酸（dTMP）生物合成的障碍严重降低了寄生虫原生动物的生存力，并且缺乏专门参与dTMP形成的酶促活性（例如dUTPase，胸苷酸合酶，二氢叶酸还原酶或胸苷激酶）导致脱氧胸苷三磷酸水平降低（三磷酸脱氧胸苷）所谓的无胸腺死亡。在此过程中，细胞核苷酸库中三磷酸脱氧尿苷（dUTP）与dTTP的比例起着至关重要的作用。高dUTP / dTTP比值导致尿嘧啶误掺入DNA，激活DNA修复途径，DNA断裂并最终导致细胞死亡。 dTMP合成的基本特征激发了人们对鉴定和开发特异性阻断与胸腺嘧啶核苷酸形成有关的生化步骤的药物的兴趣。在这里，我们综述了针对动素体（锥虫属和利什曼原虫属）和apicomplexan（疟原虫和弓形虫）原生动物胸腺嘧啶生物合成的药物发现研究的相关文献。本文介绍了有关对这些人类病原体具有抗寄生虫活性的新型抑制分子的最相关发现。

关键词: 胸苷酸的生物合成，运动塑料体，复合体，药物靶标，抑制剂，嘧啶，dTMP，抗原生动物。

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