青素结合蛋白 (PBP) 抑制剂的开发:一个10年的化学前景
Ariane F Bertonha1, Caio C L Silva1, Karina T Shirakawa1,2
1Brazilian Biosciences National Laboratory (LNBio), CNPEM, Campinas 13084-971, Brazil.
Experimental biology and medicine (Maywood, N.J.)
|November 29, 2023
概括
新的研究探索了向细菌青素结合蛋白 (PBPs) 的抑制剂,以对抗抗生素耐药性. 本综述侧重于通过检查PBP转酶域抑制剂及其结构-活性关系来开发新型抗菌剂.
科学领域:
- 微生物学与传染病的研究
- 药用化学 医学化学
- 药物发现 药物发现 药物发现
背景情况:
- 细菌细胞壁的形成,特别是糖甘 (PG) 合成,对于细菌的生存至关重要,也是抗生素的关键标.
- 青素结合蛋白 (PBPs) 是PG交叉链接中的必不可少的酶,在历史上一直是β-lactams等抗生素的目标.
- 抗生素耐药性的增加需要不断寻找具有替代作用机制的新型抗菌剂.
研究的目的:
- 审查针对PBPs的转酶域的抑制剂的近期发展.
- 讨论这些潜在的新抗生素剂的策略,设计原则和结构-活性关系 (SAR).
- 突出显示了对主要细菌病原体有活性的分子.
主要方法:
- 对过去10年发表的文章进行了全面的文献综述.
- 针对PBP转酶域的抑制剂设计的分析.
- 对已识别的化合物进行结构-活性关系 (SAR) 的评估.
主要成果:
- 一些针对PBP的新型抑制剂已经开发出来,具有潜在的治疗应用.
- 详细的SAR研究提供了关于优化抑制剂有效性和特异性的见解.
- 一些经过审查的分子对关键的细菌病原体表现出有前途的活性.
结论:
- PBP转酶域的抑制剂代表了开发新抗菌药物的有希望的途径.
- 对PBP向剂的持续研究对于应对抗生素耐药性日益增长的威胁至关重要.
- 审查的分子为下一代有效抗生素提供了潜在的线索.
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