阿维纳化物:潜在的MurA向抑制剂,用于抗甲素耐药黄金葡萄球菌 (MRSA) 中的糖糖生物合成
Ching-Ming Chang1, Jeffy Chern, Ming-Yi Chen
1Institute of Biological Chemistry, §Chemical Biology and Molecular Biophysics Program, Taiwan International Graduate Program, #Genomics Research Center, and ▽Agricultural Biotechnology Research Center, Academia Sinica , Taipei 115, Taiwan.
Journal of the American Chemical Society
|December 19, 2014
概括
来自真菌的新型阿维纳化物对抗抗甲素耐药黄金葡萄球菌 (MRSA) 具有强烈活性. 这些化合物向MurA,提供了一种针对抗生素耐药细菌的新方法,包括对菌素耐药菌株.
科学领域:
- 微生物学 微生物学
- 药用化学 医学化学
- 生物化学 生物化学
背景情况:
- 抗生素耐药性的上升,特别是耐甲基金色葡萄球菌 (MRSA),需要发现新型抗菌剂.
- 现有的抗生素面临局限性,推动研究新的治疗点和化学支架.
研究的目的:
- 识别和描述具有针对MRSA的抗菌活性的新型化合物.
- 阐明这些化合物的作用机制和药物标.
- 探索它们对抗抗生素耐药性细菌菌株的潜力.
主要方法:
- 从Neosartorya fischeri. 分离和结构阐明的avenaciolide衍生物.
- 对抗MRSA的抗微生物敏感性测试.
- (31) P核磁共振光谱和MS/MS分析以确定药物标.
- 分子模拟以了解与目标酶的相互作用.
主要成果:
- 在四种分离的阿维纳化物衍生物中,有三种 (1-4) 显示出对MRSA的显著抗菌活性.
- 发现阿维纳西奥利德可以中断细菌细胞壁生物合成.
- 确定了MurA作为药物标,其中avenaciolides 1和2对野生类型和对氏素耐药的MurA表现出活性.
- 化合物2通过分子模拟被证明可以竞争性地抑制MurA活性.
结论:
- 阿维纳西奥利德代表了一种有前途的新型抗生素类别,针对MurA.
- 这些化合物对MRSA有效,并提供了针对抗菌素耐药菌株的新机制.
- 这些发现为开发新的针对Mura的抗生素提供了基础,以对抗耐药细菌感染.
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