致病性细菌碳酸无水酶的抑制由单基甲基酸盐
Simone Giovannuzzi1, Anil Kumar Marapaka2, Nader S Abutaleb3,4
1Neurofarba Department, Pharmaceutical and Nutraceutical Section, University of Florence, Sesto Fiorentino (FI), Italy.
Journal of enzyme inhibition and medicinal chemistry
|November 23, 2023
概括
单基酸盐有效地抑制了致病性细菌中的碳酸无水酶,如尼塞利亚淋病菌和抗万科素的肠球菌. 化合物13显示出作为抗菌剂对抗N. gonorrhoeae的潜力.
科学领域:
- 生物化学 生物化学
- 药用化学 医学化学
- 抗菌研究 抗菌研究
背景情况:
- 来自致病细菌的碳酸 anhydrases (CA),如尼塞利亚淋病和抗万科胺素抗性肠球菌 (VRE) 是已验证的抗菌药物标.
- 探索这些细菌CA的新型抑制剂对于开发新的抗菌疗法至关重要.
研究的目的:
- 调查单基甲酸盐 (MTC) 对来自N. gonorrhoeae (α-NgCA) 和Enterococcus faecium (α-EfCA和γ-EfCA) 的碳酸无水体的抑制潜力.
- 评估MTCs对N. gonorrhoeae和VRE.临床分离物的抗菌活性.
主要方法:
- 酶抑制试验使用纯化的α-NgCA,α-EfCA和γ-EfCA与一个MTC小组进行.
- 对于每个化合物和酶相互作用,确定了体外抑制常量 (KI).
- 用选择的MTCs对N. gonorrhoeae和VRE的临床菌株进行了抗菌感应性测试.
主要成果:
- MTCs在体外显示出显著的α-NgCA抑制,KI值在0.367至0.919μM之间.
- α-EfCA和γ-EfCA也被MTC强烈抑制,KI范围分别为0.1950.959 μM和0.1491.90 μM.
- 化合物13对N. gonorrhoeae菌株 (1664μg/mL) 具有抗菌活性,但对VRE菌株没有观察到增长抑制.
结论:
- 单甲基酸盐是来自N. gonorrhoeae和E. faecium的细菌碳酸无水酶的有效抑制剂.
- 化合物13作为一种主要化合物,可用于开发专门针对N. gonorrhoeae感染的新抗菌剂.
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