阿里尼科利德家族的宏化物提供了一种新的治疗,用于打击抗药性结核病
Sunghoon Hwang1, Bo Eun Heo2, Thanh Quang Nguyen2
1Natural Products Research Institute, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, 08826, Seoul, Republic of Korea.
Angewandte Chemie (International ed. in English)
|October 14, 2024
概括
研究人员发现了来自甲虫肠道细菌的新化合物 - - arenicolides D-K. 阿瑞尼科利德A (Ar-A) 对抗多耐药结核病 (MDR-TB) 和广泛耐药结核病 (XDR-TB) 显示出强烈的活性.
科学领域:
- 自然产品化学 自然产品化学
- 微生物学 微生物学
- 药用化学 医学化学
背景情况:
- 耐多药 (MDR) 和广泛耐药 (XDR) 的结核菌菌菌株 (Mtb) 构成了全球卫生面临的重大挑战.
- 发现新型抗菌剂对于对抗耐药结核病至关重要.
研究的目的:
- 识别和描述具有针对MDR和XDR-Mtb活动的新化学实体.
- 阐明有前途的化合物的结构和作用机制.
主要方法:
- 对Micromonospora sp.进行化学研究. GR10导致分离了八种新的烯化物和烯化物A (Ar-A).
- 用基因组分析,基于量子力学的计算,化学衍生和生物信息分析来建立绝对立体化学.
- 使用了体外抗菌试验,机理学研究 (ATP耗尽,细胞壁不稳定),巨细胞感染模型和体内小鼠模型.
主要成果:
- 发现了8种新的烯化物 (Ar-D-K) 和Ar-A. 他们的绝对立体化学是完全阐明.
- 在体外,Ar-A对MDR和XDR-Mtb.表现出强大的抗菌活性.
- 在Ar-A诱导的ATP枯竭,破坏了Mtb细胞壁的稳定性,在巨细胞中表现出有效性,并在小鼠模型中与阿米卡辛表现出协同效应.
结论:
- Ar-A 是治疗耐药结核病的一种有前途的药物.
- 这些发现凸显了微生物来源的天然产品在开发新的抗结核病疗法方面的潜力.
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