通过准替代性全位,在细菌糖解酶中进行有效的药物设计选
Ipek Turkmenoglu1, Gamze Kurtulus1, Cenk Sesal2
1Department of Biology, Marmara University, Institute of Pure and Applied Sciences, 34722, Kadıköy, İstanbul, Turkey.
Archives of biochemistry and biophysics
|November 1, 2024
概括
研究人员对FDA批准的药物进行了选,这些药物针对Staphylococcus aureus糖溶性酶的全位. 四种化合物表现出抗菌活性,其中两种有效对抗金黄色菌株,这表明一种新的药物开发策略.
科学领域:
- 微生物学 微生物学
- 生物化学 生化学
- 药物发现 药物发现 药物发现
背景情况:
- 黄金葡萄球菌 (Staphylococcus aureus) 由于抗生素耐药性而构成重大威胁.
- 准像糖溶性酶这样的重要细菌酶提供了一个潜在的治疗途径.
- 与催化场所相比,保护程度较差的化场所为选择性药物向提供了机会.
研究的目的:
- 通过向全位,识别FDA批准的化合物,可以通过向全位来选择性抑制金黄色葡萄球菌的糖分酶 (PFK,GADPH,PK).
- 评估针对S. aureus的已识别的候选药物的抗菌活性和酶抑制.
主要方法:
- 虚拟选7229种化合物,包括1416种FDA批准的药物,对使用分子对接的三种S. aureus甘化酶的七个全位进行选.
- 对抗菌生长抑制和酶活性的顶级候选药物的体外测试.
- 评估有前途的化合物的有效性,以对甲素敏感和甲素耐药的金黄色细菌菌株.
主要成果:
- 四种化合物 (Candesartan cilexetil,Montelukast,Dronedarone,Thonzonium) 显示出显著的抗菌增长抑制 (>40%).
- 坎德沙坦基莱克塞提尔和松在低度 (0.5-4微克/毫升) 时,对金黄色菌株具有很高的杀死效率.
- 对一些化合物在体外杀死疗效和酶抑制试验之间观察到差异.
结论:
- 准糖解酶的全位是发现新型抗菌剂的可行策略.
- 坎德沙坦西莱克塞特和索尼有潜力作为S. aureus感染的化合物.
- 未来的策略应该考虑针对糖解酶的组合,以提高疗效.
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