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Review Article

自由生活变形虫新药发现的创新方法

卷 20, 期 1, 2019

页: [60 - 69] 页: 10

弟呕挨: 10.2174/1389450119666180426100452

价格: $65

摘要

尽管在药物发现和化疗方案改进方面取得了进展，但由免费生活的阿米巴(Fla)引起的人类感染死亡率很高(~95%)。引起人脑致死性感染的FLA主要有马尾藻(NaegleriaFowleri)、曼氏Balamuthia mandrillaris和棘阿米巴。新的药物靶点的发现仍然是唯一可行的选择，以解决这些中枢神经系统(CNS)感染，以降低死亡率引起的佛罗里达州。在这些Fla中，N.fowleri可引起原发性阿米巴脑膜脑炎(PAM)，而蓖麻黄和曼氏B.mandrillaris则可引起肉芽肿性阿米巴脑炎(GAE)。Fla引起的感染用利福平、氟康唑、两性霉素-B和米尔特福辛等药物治疗。米替福辛是一种抗利什曼药，也是一种实验性的抗癌药物.虽然只有罕见的成功病例，但这些药物仍然未能降低由Fla引起的脑感染的死亡率。最近，借助生物信息学计算工具和发现的FLA基因组数据，发现新的药物靶点已经成为可能。这些细胞靶点要么是Fla特有的蛋白质，要么是人类和这些单细胞真核生物之间共享的蛋白质。后一类蛋白质已被证明是FDA批准的非传染性疾病药物的靶点。本综述概述了可用于发现此类新药物靶点的生物信息学方法、过去进行的体外试验的历史记录以及这些目标在Fla引起的人类疾病中的翻译价值。

关键词: 药物靶点发现，无菌阿米巴，棘球虫，曼氏巴拉穆，结构活性关系。

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