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An Efficient Method for the Synthesis of Peptoids with Mixed Lysine-type/Arginine-type Monomers and Evaluation of Their Anti-leishmanial Activity
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作为抗菌剂的二甲酸.

Ghayah Bahatheg1, Rajesh Kuppusamy2, Muhammad Yasir3

  • 1School of Chemistry, The University of New South Wales (UNSW), Sydney, NSW 2052, Australia; Department of Chemistry, Faculty of Science, University of Jeddah, Jeddah 21589, Saudi Arabia.

Bioorganic chemistry
|April 7, 2024
PubMed
概括

新的二次性类体显示出广泛的抗菌活性,对抗阳性和阴性细菌. 这些化合物破坏细菌细胞膜和低毒性的生物膜,为新型抗菌药物开发提供了潜力.

关键词:
抗生物膜是一种抗生物膜.抗菌剂 抗菌剂 抗菌剂膜破坏破坏 膜破坏可以模仿.类蛋白质 (peptoids) 是一种蛋白质.

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科学领域:

  • 药用化学 医学化学
  • 抗菌研究 抗菌研究
  • 生物材料科学 生物材料科学

背景情况:

  • 之前的类抗菌药物只对格拉姆阳性细菌有效.
  • 需要新型抗菌剂,有效对抗更广泛的病原体,包括阴性细菌.
  • 了解类的结构-活性关系对于开发强大的抗微生物化合物至关重要.

研究的目的:

  • 合成和评估新型二面性类化合物对抗 Gram 阳性和 Gram 阴性病原体的抗菌活性.
  • 研究这些类的作用机制,重点关注细菌细胞膜破坏.
  • 评估这些化合物的破坏细菌生物膜的潜力及其对哺乳动物细胞的毒性.

主要方法:

  • 合成34个具有不同疏水性和离子性部分的二元性类化合物.
  • 使用最小抑制度 (MIC) 测定对标准细菌菌株进行抗微生物敏感性测试.
  • 作用机制研究包括绑定双层脂质膜 (tBLMs) 和细胞质膜透性测试.
  • 生物膜破坏测定和对红细胞的细胞毒性评估.

主要成果:

  • 一种甲二度瓜尼迪尼类 (10j) 显示出对*S. aureus*和*E. coli* (MIC分别为0.8和6.2微克/毫升) 的强烈活性.
  • 发现类药物会破坏细菌细胞膜,这表明其主要的作用机制.
  • 几种化合物对哺乳动物红细胞的毒性可以忽略不计.
  • 乙烯和八-纳-瓜尼迪尼类 (10c和10k) 有效地破坏了已建立的*S. aureus*生物膜.

结论:

  • 具有优化的疏水性和离子性的二元性类体表现出广泛的抗菌活性.
  • 这些化合物通过破坏细菌细胞膜而起作用,并显示出对抗生物膜的前景.
  • 开发的类代表了一类新的潜在抗菌剂,具有低哺乳动物毒性.