Kowalczyk Paweł, Trzepizur Damian, Szymczak Mateusz, Skiba Grzegorz, Kramkowski Karol, Ostaszewski Ryszard
Department of Animal Nutrition, The Kielanowski Institute of Animal Physiology and Nutrition, Polish Academy of Sciences, 05-110 Jabłonna, Poland.
Institute of Organic Chemistry PAS, Kasprzaka 44/52, 01-224 Warsaw, Poland.
Materials (Basel). 2021 Feb 22;14(4):1025. doi: 10.3390/ma14041025.
An initial study of 1,2-diarylethanols derivatives as new potential antibacterial drugs candidates was conducted. Particular emphasis was placed on the selection of the structure of 1,2-diarylethanols with the highest biological activity of lipopolysaccharides (LPS) in the model strains of Escherichia coli K12 (without LPS in its structure) and R2-R4 (with different lengths of LPS in its structure). In the presented studies, based on the conducted minimum inhibitory concentration (MIC) and MBC tests, it was demonstrated that the antibacterial (toxic) effect of 1,2-diarylethanols depends on their structure and the length of LPS bacteria in the membrane of specific strains. Moreover, the oxidative damage of bacterial DNA isolated from bacteria after modification with newly synthesized compounds after application of the repair enzyme Fpg glycosylases was analysed. The analysed damage values were compared with modification with appropriate antibiotics; bacterial DNA after the use of kanamycin, streptomycin, ciprofloxacin, bleomycin and cloxicillin. The presented research clearly shows that 1,2-diarylethanol derivatives can be used as potential candidates for substitutes for new drugs, e.g., the analysed antibiotics. Their chemical and biological activity is related to two aromatic groups and the corresponding chemical groups in the structure of the substituent. The observed results are particularly important in the case of increasing bacterial resistance to various drugs and antibiotics, especially in nosocomial infections and neoplasms, and in the era of pandemics caused by microorganisms.
对1,2 - 二芳基乙醇衍生物作为新型潜在抗菌药物候选物进行了初步研究。特别强调了在大肠杆菌K12（其结构中无脂多糖）和R2 - R4（其结构中有不同长度脂多糖）的模型菌株中选择具有最高脂多糖（LPS）生物活性的1,2 - 二芳基乙醇结构。在本研究中，基于所进行的最低抑菌浓度（MIC）和MBC测试，证明了1,2 - 二芳基乙醇的抗菌（毒性）作用取决于其结构以及特定菌株膜中LPS细菌的长度。此外，在应用修复酶Fpg糖基化酶后，分析了用新合成化合物修饰后从细菌中分离出的细菌DNA的氧化损伤。将分析的损伤值与用适当抗生素修饰的情况进行比较；使用卡那霉素、链霉素、环丙沙星、博来霉素和氯唑西林后的细菌DNA。本研究清楚地表明，1,2 - 二芳基乙醇衍生物可作为新药替代品的潜在候选物，例如所分析的抗生素。它们的化学和生物活性与两个芳环基团以及取代基结构中的相应化学基团有关。在细菌对各种药物和抗生素的耐药性增加的情况下，特别是在医院感染和肿瘤中，以及在微生物引起的大流行时代，观察到的结果尤为重要。
