非自然内型B PPAP作为新型化合物,具有对Mycobacterium tuberculosis的活性
Philipp Peslalz1, Mark Grieshober2, Frank Kraus3
1Chair of Organic Chemistry, Faculty of Chemistry and Food Chemistry, Technical University Dresden, Bergstr. 66, Dresden01069 ,Germany.
Journal of medicinal chemistry
|October 12, 2023
概括
新的多聚基聚环酸 (PPAP) 显示出对抗耐药结核病 (TB) 的强有力的活性. 这些稳定的化合物,特别是PPAP53,提供了一种有前途的新型抗菌药物,用于对抗耐药的Mycobacterium结核病菌株.
科学领域:
- 药用化学 医学化学
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 由Mycobacterium tuberculosis (Mtb) 引起的结核病 (TB) 是COVID-19前的主要传染病死亡原因.
- 耐药的Mtb菌株需要开发新的抗菌菌剂.
- 一种天然化合物 - - 超林 (Hyperforin) 显示出Mtb的活性,但却存在不稳定性.
研究的目的:
- 开发具有增强抗菌菌效能的稳定类型的高福林.
- 从新一类化合物中识别和描述新的抗结核病候选药物.
- 评估化合物的体外活性和安全概况,以对抗Mtb.
主要方法:
- 合成和表征B型聚烯酸聚环酸黄醇 (PPAP) 的照片和实验室稳定性.
- 评估PPAP对毒性和耐药的Mtb菌株 (细胞外和细胞内) 的抗菌活性.
- 使用初级人类巨细胞和体外药物代谢研究 (CYP诱导,PXR相互作用) 评估化合物细胞毒性.
主要成果:
- 开发出稳定的B型PPAP,与hyperforin相比,其抗菌有效性得到改善.
- 确定了PPAP22作为一种化合物,其盐PPAP53显示出增强的溶解性和强大的Mtb生长抑制.
- PPAP53在对抗药物耐药的Mtb菌株的治疗中表现出有效性,而不损害人类巨细胞,并且在体外表现出有利的代谢性质.
结论:
- B型PPAP是一种新型的抗菌菌化合物.
- PPAP53具有显著的潜力作为治疗药物敏感和耐药结核病的治疗剂.
- 由于PPAP53具有有利的生物物理和抗菌素特性,因此需要进一步研究临床开发.
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