Pałkowski Łukasz, Błaszczyński Jerzy, Skrzypczak Andrzej, Błaszczak Jan, Kozakowska Karolina, Wróblewska Joanna, Kożuszko Sylwia, Gospodarek Eugenia, Krysiński Jerzy, Słowiński Roman
Department of Pharmaceutical Technology, Nicolaus Copernicus University, Jurasza 2, 85-094, Bydgoszcz, Poland.
Chem Biol Drug Des. 2014 Mar;83(3):278-88. doi: 10.1111/cbdd.12236. Epub 2013 Dec 26.
A series of 70 new 3,3'(α,ω-dioxaalkyl)bis(1-alkylimidazolium) chlorides were synthesized. They were characterized with respect to surface active properties and antimicrobial activity against the following pathogens: Staphylococcus aureus, Enterococcus faecalis, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Pseudomonas aeruginosa, Candida krusei, and Candida albicans. In this article, besides description of the synthesis, we characterize a set of features of these compounds, concerning their structure (described by the length of the dioxaalkan spacer and the length of the alkyl substituent in the aromatic ring) and surface active properties (critical micelle concentration, value of surface tension at critical micelle concentration, value of surface excess, molecular area of a single particle, and free energy of adsorption of molecule). Then, we present a SAR study for Staphylococcus aureus, as one of the most widespread pathogenic strains, conducted with the help of the Dominance-based Rough Set Approach (DRSA), that involves identification of relevant features and relevant combinations of features being in strong relationship with a high antimicrobial activity of the compounds. The SAR study shows, moreover, that the antimicrobial activity is dependent on the type of substituents and their position at the chloride moiety, as well as on the surface active properties of the compounds.
合成了一系列70种新型的3,3'(α,ω-二氧杂烷基)双(1-烷基咪唑鎓)氯化物。对它们的表面活性性质以及针对以下病原体的抗菌活性进行了表征：金黄色葡萄球菌、粪肠球菌、鲍曼不动杆菌、大肠杆菌、肺炎克雷伯菌、阴沟肠杆菌、铜绿假单胞菌、克鲁斯念珠菌和白色念珠菌。在本文中，除了描述合成过程外，我们还表征了这些化合物的一组特征，涉及它们的结构（由二氧杂烷间隔基的长度和芳环中烷基取代基的长度描述）和表面活性性质（临界胶束浓度、临界胶束浓度下的表面张力值、表面过剩值、单个颗粒的分子面积以及分子的吸附自由能）。然后，我们以金黄色葡萄球菌作为最广泛传播的致病菌株之一，借助基于优势关系的粗糙集方法（DRSA）进行了构效关系研究，该研究涉及识别与化合物的高抗菌活性有强关系的相关特征和相关特征组合。此外，构效关系研究表明，抗菌活性取决于取代基的类型及其在氯化物部分的位置，以及化合物的表面活性性质。
