一种用于治疗结核病的小分子尼特罗伊米达佐皮兰候选药物
C K Stover1, P Warrener, D R VanDevanter
1PathoGenesis Corporation, Seattle, Washington 98119, USA. kstover@pathogenesis.com
Nature
|July 6, 2000
概括
新的尼特罗伊米达佐皮兰化合物显示出对Mycobacterium tuberculosis的强有力的活性. 这些化合物杀死复制和休眠的细菌,为结核病提供了有前途的新治疗方法,包括多药耐药菌株.
科学领域:
- 药用化学 医学化学
- 微生物学 微生物学
- 传染性疾病 传染性疾病
背景情况:
- 结核病 (TB) 仍然是全球主要的传染性死亡原因,数百万人感染了结核菌菌.
- 多药耐药结核病的增加及其与艾滋病病毒的协同作用凸显了对新型抗结核药物的迫切需要.
- 30多年来,没有开发出具有新机制的新型结核病药物.
研究的目的:
- 发现和描述具有抗结核活性的新型化合物.
- 研究这些新化合物的作用机制.
- 评估它们对抗耐药和潜伏形式的M.结核病的疗效.
主要方法:
- 合成尼特罗伊米达佐皮兰化合物.
- 在体外测试抗结核活性,包括针对复制和静态的M.结核病.
- 对作用机制的评估,涉及M.结核病F420辅因子.
- 在动物模型中对化合物PA-824的体内评估.
主要成果:
- 一系列的尼特罗伊米达佐皮兰化合物显示出显著的抗结核活性.
- 化合物被M.结核病F420辅因子激活,抑制蛋白质和细胞壁脂质合成.
- 尼特罗伊米达索皮兰 (Nitroimidazopyrans) 对复制性和静态性M.结核病具有杀菌活性.
- 化合物PA-824在动物模型中显示出对抗多药耐药的M.结核病的强有力的活性和良好的口服生物可用性.
结论:
- 尼特罗伊米达索皮兰 (Nitroimidazopyrans) 是一种具有结核病治疗潜力的新型小分子类.
- 这些化合物对各种M.结核病种群具有杀菌活性,包括休眠和耐药菌株.
- 进一步开发尼特罗伊米达索皮兰可以解决对新的结核病治疗方法的关键未满足需求.
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