4.4 Article

Practical Synthesis of Polyamine Succinamides and Branched Polyamines

期刊

CHEMISTRYOPEN
卷 11, 期 10, 页码 -

出版社

WILEY-V C H VERLAG GMBH
DOI: 10.1002/open.202200147

关键词

antibiotics; polyamines; spermine; succinic anhydride; thermine

资金

  1. Government of the Kingdom of Saudi Arabia
  2. GW4 Generator Award [GW4-GF2-015]
  3. University of Bath Alumni Fund [026 F1920B]

向作者/读者索取更多资源

Antibiotic resistance poses an increasingly serious threat to human health, and the lack of new antibiotics exacerbates this issue. This study presents a practical synthesis method for potential new antibiotics, capable of combating various bacteria including MRSA and Pseudomonas aeruginosa. By utilizing specific synthesis techniques, the antimicrobial activity of the antibiotics can be enhanced.
Antibiotic resistance is now a growing threat to human health, further exacerbated by the lack of new antibiotics. We describe the practical synthesis of a series of substituted polyamine succinamides and branched polyamines that are potential new antibiotics against both Gram-positive and Gram-negative bacteria, including MRSA and Pseudomonas aeruginosa. They are prepared via 1,4-Michael addition of acrylonitrile and then hydrogenation of the nitrile functional groups to primary amines. They are built upon the framework of the naturally occurring polyamines thermine (3.3.3, norspermine) and spermine (3.4.3), homo- and heterodimeric polyamine succinic amides. Linking two of the same or different polyamines together via amide bonds can be achieved by introducing a carboxylic acid group on the first polyamine, then coupling that released carboxylic acid to a free primary amine in the second polyamine. If the addition of positive charges on the amino groups along the polyamine chains are a key factor in their antimicrobial activity against Gram-negative bacteria, then increasing them will increase the antimicrobial activity. Synthesising polyamine amide dimers will increase the total net positive charge compared to their monomers. The design and practical synthesis of such homo- and hetero-dimers of linear polyamines, spermine and norspermine, are reported. Several of these compounds do not display significant antibacterial activity against Gram-positive or Gram-negative bacteria, including MRSA and Pseudomonas aeruginosa. However, the most charged analogue, a branched polyamine carrying eight positive charges at physiological pH, displays antibiofilm activity with a 50 % reduction in PAO1 at 16-32 mu g mL(-1).

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.4
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据