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一种乙烯基-ACP还原酶抑制剂,NITD-916,表达了抗Mycobacterium的活性

Yaping Jia^1,2, Junsheng Fan^1,2, Zhili Tan^1,2

¹Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine,Tongji University, Shanghai, China.

Antimicrobial agents and chemotherapy

|May 23, 2025

概括

NITD-916是一种-ACP减少酶抑制剂,在体外和体内有效地抑制了Mycobacterium的生长. 这种新型化合物显示出治疗具有挑战性的M.瘤感染的潜力,即使在巨和小鼠模型中也是如此.

科学领域:

微生物学微生物学
传染性疾病传染性疾病
药物发现药物发现药物发现

背景情况:

由于广泛的抗微生物药物耐药性,mycobacterium疹感染带来了重大治疗挑战.
现有的疗法通常有效性有限,需要开发新的治疗药物.
基-ACP减少酶抑制剂代表了针对菌根菌体生长的一类有前途的化合物.

研究的目的:

为了评估NITD-916的体外和体内疗效,一个基-ACP还原酶抑制剂,对Mycobacterium.
确定NITD-916与现有抗生素的抗菌活性谱和协同作用潜力.
评估M. abscessus感染的临床前模型中NITD-916的治疗效果.

主要方法:

对临床M. abscessus分离物和使用微稀释的参考菌株确定了NITD-916的最小抑制度 (MIC).
药物兼容性和协同效应通过10种临床重要抗生素的棋盘测定来评估.
试验室活性在培养的巨细胞中进行了测试,体内疗效在急性肺M.瘤感染的小鼠模型中进行了评估.

主要成果:

NITD-916显示对M.的细菌静止活性,MIC50为0.125 mg/L,MIC90为1 mg/L.
观察到NITD-916和澄素之间对M. abscessus亚种的一个子集产生协同效应. 马西里昂斯品种. 马西里昂斯品种.
在体内,14天服用100mg/kgNITD-916可显著降低小鼠肺中的细菌负荷5.6 log10 CFU.

结论:

在体外和体内,NITD-916对Mycobacterium abscessus表现出强大的活性.
该化合物显示出作为M.病的治疗剂的潜力,可能是组合疗法.
对NITD-916进行进一步的研究是有必要的,因为它对抗具有挑战性的真菌细菌感染的临床开发是有必要的.

关键词:

这种细菌是Mycobacterium abscessus.这是NITD-91616中的一个.在NTM中,NTM是NTM.抗微生物活性的抗微生物活性.埃诺伊尔-ACP减少酶抑制剂

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