PEGylated Bis-Quaternary Triphenyl-Phosphonium Tosylate Allows for Balanced Antibacterial Activity and Cytotoxicity,ACS Applied Bio Materials

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PEGylated Bis-Quaternary Triphenyl-Phosphonium Tosylate Allows for Balanced Antibacterial Activity and Cytotoxicity
ACS Applied Bio Materials ( IF 4.6 ) Pub Date : 2020-08-17 , DOI: 10.1021/acsabm.0c00837
Qiqi Lei ₁ , Xuexu Lai ₁ , Yuwei Zhang ₁ , Zhou Li ₁ , Riwang Li ₁ , Wenning Zhang ₁ , Ningjian Ao ₁ , Hong Zhang ₁

Affiliation

Quaternary triphenylphosphonium compounds (TPP⁺) have been widely recognized as an important antimicrobial because of their fast antimicrobial speed and broad antimicrobial spectrum. However, small-molecule TPP⁺ compounds have the defects of toxicity, which is the key factor that limits their practical applications. Here, two mono- and one bis-quaternary phosphonium tosylate compounds with different lengths of oligo(ethylene glycol) (OEG) chains and TPP⁺ as the active moiety were synthesized. Bis-TPP⁺ have a short OEG chain coupling two TPP⁺ at both ends, while mono-TPP⁺ attaches the OEG chain at one end in one molecule. In vitro antibacterial activities were evaluated against both Gram-positive as well as Gram-negative bacteria in terms of the inhibition zone (ZOI) and minimum inhibitory concentration (MIC). To investigate the antibacterial mechanism, β-galactosidase activity was monitored for measuring the degree of membrane permeability correlated to the abilities to disrupt the membranes of bacteria. Moreover, their structure–antibacterial activity and structure–cytotoxicity relationships were further analyzed. The results indicated that bis-TPP⁺ synthesized can reach the sterilization rate 90% or more against Escherichia coli and Staphylococcus aureus at MICs of 3.1 and 1.5 mg/mL, respectively, and meanwhile, the cell proliferation can reach more than 80%. This paper represents an excellent approach for development of bis-TPP⁺ bactericidal molecules that would achieve an optimal balance between antimicrobial activity and cytotoxicity.

中文翻译：

聚乙二醇化双季三苯基-甲苯磺酸鏻可实现平衡的抗菌活性和细胞毒性

季三苯基鏻化合物（TPP ⁺）因其抗菌速度快、抗菌谱广而被广泛认为是一种重要的抗菌剂。然而，小分子TPP ⁺化合物存在毒性的缺陷，这是限制其实际应用的关键因素。在这里，合成了两种具有不同长度的寡（乙二醇）（OEG）链和TPP ⁺作为活性部分的单季和一种双季铵甲苯磺酸盐化合物。Bis-TPP ⁺有一条短的 OEG 链，在两端连接两个 TPP ^{+ ，而 mono-TPP}⁺在一个分子的一端连接 OEG 链。体外根据抑菌圈 (ZOI) 和最低抑菌浓度 (MIC) 评估对革兰氏阳性菌和革兰氏阴性菌的抗菌活性。为了研究抗菌机制，监测β-半乳糖苷酶活性以测量与破坏细菌膜的能力相关的膜通透性程度。此外，进一步分析了它们的结构-抗菌活性和结构-细胞毒性关系。结果表明合成的bis-TPP ^+对大肠杆菌和金黄色葡萄球菌的杀菌率可达90%以上。MIC分别为3.1和1.5 mg/mL，同时细胞增殖率可达80%以上。本文代表了一种开发双 TPP ⁺杀菌分子的绝佳方法，该分子将在抗菌活性和细胞毒性之间实现最佳平衡。

更新日期：2020-09-21

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