探索利醇的新型利/异利异醇对抗多药耐药细菌的研究
Mariam Omara1, Mohamed Hagras2, Mohamed M Elsebaie2
1Department of Pharmaceutical Organic Chemistry, College of Pharmacy (Girls), Al-Azhar University Cairo Egypt.
RSC advances
|July 10, 2023
概括
新型甲衍生物对包括MRSA在内的多药耐药细菌表现出强大的抗菌活性. 化合物15d在体外和体内表现出显著的疗效,为打击抗菌素耐药性提供了一个有希望的新途径.
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:
- 抗菌素耐药性 (AMR) 是一个重大的全球健康威胁,需要开发新的治疗药物.
- 乙醇支架已经成为一种有前途的化合物类别,用于对抗耐药细菌,特别是葡萄球菌.
- 结构-活性关系 (SAR) 研究确定了抗菌疗效的基本特征,包括瓜尼丁头和脂性尾巴.
研究的目的:
- 合成和评估一系列新型的乙衍生物,以探索对脂性部分的修改.
- 识别具有强大抗多药耐药性 (MDR) 格拉姆阳性细菌的新型化合物,包括耐美西林*金黄色葡萄球菌* (MRSA).
- 评估最有前途的候选药物的体外和体内疗效和初步毒性.
主要方法:
- 使用苏苏基合反应合成了23种基酸衍生物.
- 在实验室中对抗菌活性进行了评估,对比一组临床分离物,包括对美西林敏感的*金黄色葡萄球菌* (MSSA),MRSA和抗胺素的*金黄色葡萄球菌* (VRSA).
- 确定了最小抑制度 (MIC),并使用小鼠皮肤感染模型在体内进一步评估有前途的化合物,并使用Caco-2细胞在体内检测细胞毒性.
主要成果:
- 化合物7d,15d和17d对MRSA USA300具有强烈的MIC值.
- 化合物15d表现出优异的活性,在0.5μg/ml的剂量下抑制MRSA USA400 (两倍于胺素) 并显示出低MIC对各种耐药菌株,包括对线胺素耐药MRSA和对胺素耐药分离物.
- 化合物15d在MRSA皮肤感染模型中有效降低了体内细菌负担,并表现出良好的毒性特征,在测试度下,Caco-2细胞中的细胞活力为100%.
结论:
- 合成的乙衍生物代表了一种有前途的新型抗生素类别,对具有挑战性的格拉姆阳性病原体有效.
- 化合物15d在体外和体内具有显著的抗菌潜力,需要进一步开发作为对抗抗性 * 葡萄球菌 * 感染的治疗剂.
- 良好的安全性概况表明,这些化合物可以为现有的抗微生物药物耐药性治疗提供可行的替代方案.
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