Faculty of Medicine, St. Kliment Ohridski University of Sofia, 1 Kozyak Str, 1407, Sofia, Bulgaria.
J Membr Biol. 2020 Jun;253(3):247-256. doi: 10.1007/s00232-020-00121-6. Epub 2020 May 11.
The increasing resistance of many pathogens to most of the common antimicrobials requires the development of new substances with more effective antimicrobial properties. In the present work, we investigated the mechanism of the antimicrobial activity of novel water soluble ammonium quaternary benzanthrone (Compound B) on model membranes, composed of dipalmitoylphosphatidylcholine, 1-palmitoyl-2-oleoylphosphatidylcholine, dipalmitoylphosphatidylglycerol, 1-palmitoyl-2-oleoylphosphatidylglycerol, and dipalmitoylphosphatidylethanolamine (DPPE). The lipids were chosen to represent a model of a bacterial membrane. The changes in surface pressure of the model membranes, before and after the addition of Compound B, were studied by the Langmuir's monolayer method, and the compressional modulus for each monolayer was determined. In addition, the surface morphology of the lipid monolayers before and after injection of Compound B was monitored by Brewster Angle Microscopy. The results showed that Compound B penetrated all the monolayers studied. The most noticeable effects were found with the negatively charged phosphatidylglycerols and with DPPE leading to the conclusion that the electrostatic interactions between the compound and the lipid head groups and the possible formation of hydrogen bonds between the amino group of the ethanolamine and the keto groups in the structure of Compound B are of great importance. In addition, the penetration ability of the benzoquinone with all phospholipids studied was stable even at higher values of the surface pressure, i.e. thicker monolayers, due to the hydrophobic interaction, which plays also an important role for the antimicrobial activity of Compound B.
由于许多病原体对大多数常见抗生素的耐药性不断增强,因此需要开发具有更强抗菌特性的新物质。在本工作中,我们研究了新型水溶性铵季𬭸苯并蒽酮(化合物 B)对由二棕榈酰磷脂酰胆碱、1-棕榈酰-2-油酰磷脂酰胆碱、二棕榈酰磷脂酰甘油、1-棕榈酰-2-油酰磷脂酰甘油和二棕榈酰磷脂酰乙醇胺(DPPE)组成的模型膜的抗菌活性的作用机制。选择这些脂质来代表细菌膜的模型。通过 Langmuir 单层法研究了模型膜在添加化合物 B 前后的表面压力变化,并确定了每个单层的压缩模量。此外,通过布鲁斯特角显微镜监测了注入化合物 B 前后脂质单层的表面形态。结果表明,化合物 B 穿透了所有研究的单层。在带负电荷的磷脂酰甘油和 DPPE 中观察到最明显的效果,这表明化合物与脂质头部基团之间的静电相互作用以及氨基与化合物 B 结构中的酮基之间可能形成氢键非常重要。此外,由于疏水性相互作用,苯并醌对所有研究的磷脂的穿透能力即使在较高的表面压力下(即较厚的单层)也很稳定,这对化合物 B 的抗菌活性也起着重要作用。