调整邻氨基苯甲酰胺肽模拟物设计以选择性靶向浮游细菌和生物膜。

Kuppusamy Rajesh, Yasir Muhammad, Yu Tsz Tin, Voli Florida, Vittorio Orazio, Miller Michael J, Lewis Peter, Black David StC, Willcox Mark, Kumar Naresh

School of Chemistry, The University of New South Wales (UNSW), Sydney, NSW 2052, Australia.

School of Optometry and Vision Science, The University of New South Wales (UNSW), Sydney, NSW 2052, Australia.

Antibiotics (Basel). 2023 Mar 15;12(3):585. doi: 10.3390/antibiotics12030585.

There is a pressing need to develop new antimicrobials to help combat the increase in antibiotic resistance that is occurring worldwide. In the current research, short amphiphilic antibacterial and antibiofilm agents were produced by tuning the hydrophobic and cationic groups of anthranilamide peptidomimetics. The attachment of a lysine cationic group at the tail position increased activity against by >16-fold (from >125 μM to 15.6 μM) and greatly reduced cytotoxicity against mammalian cells (from ≤20 μM to ≥150 μM). These compounds showed significant disruption of preformed biofilms of at micromolar concentrations.

迫切需要开发新型抗菌药物，以应对全球范围内抗生素耐药性不断增加的问题。在当前的研究中，通过调节邻氨基苯甲酰胺拟肽的疏水基团和阳离子基团，制备了短链两亲性抗菌和抗生物膜剂。在尾部位置连接赖氨酸阳离子基团，使对[具体对象未提及]的活性提高了16倍以上（从>125μM降至15.6μM），并大大降低了对哺乳动物细胞的细胞毒性（从≤20μM升至≥150μM）。这些化合物在微摩尔浓度下对[具体对象未提及]预先形成的生物膜具有显著的破坏作用。