Prediction of Antifungal Activity of Gemini Imidazolium Compounds

Abstract

The progress of antimicrobial therapy contributes to the development of strains of fungi resistant to antimicrobial drugs. Since cationic surfactants have been described as good antifungals, we present a SAR study of a novel homologous series of 140 bis-quaternary imidazolium chlorides and analyze them with respect to their biological activity against Candida albicans as one of the major opportunistic pathogens causing a wide spectrum of diseases in human beings. We characterize a set of features of these compounds, concerning their structure, molecular descriptors, and surface active properties. SAR study was conducted with the help of the Dominance-Based Rough Set Approach (DRSA), which involves identification of relevant features and relevant combinations of features being in strong relationship with a high antifungal activity of the compounds. The SAR study shows, moreover, that the antifungal 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. We also show that molecular descriptors MlogP, HOMO-LUMO gap, total structure connectivity index, and Wiener index may be useful in prediction of antifungal activity of new chemical compounds.

Antimicrobial and Cytotoxic Activity of Novel Imidazolium-Based Ionic Liquids

“…In recent years, our team has studied the synthesis, biological and surface activity, and structure–activity relationships (SAR) of quaternary ammonium salts. In the scope of our interest are mainly mono- and bis-imidazolium salts [ 15 , 16 , 17 ]. We found that the following structures of bis-imidazolium chlorides have the optimal antimicrobial activity: 3,3’- (α, ω-dioxaalkane) bis (1-alkylimidazolium chloride), which has at least six carbon atoms in its linker, and has a R substituent of C7 to C11; α, ω-bis [(alkane) imidazol-1-yl-3-alkoxymethyl] chloride, which has at least five carbon atoms in the linker, and has a C7 to C13; and 3,3’- (α, ω-dioxaalkane) bis (1-alkylimidazolium) chloride or α, ω-bis [(alkane) imidazol-1-yl-3- alkoxymethyl chloride], which has at least seven carbon atoms and has a substituent R of C7 to C11.…”

Structure-Activity Relationships of the Imidazolium Compounds as Antibacterials of Staphylococcus aureus and Pseudomonas aeruginosa

“…The analyzed information system was divided randomly into a training and a test set, according to stratified cross-validation scheme, in a ratio of 4 to 1, i.e., 5-fold cross-validation [ 29 ]. Decision rules induced from the training set were checked on the validation set.…”

Perspective Chapter: Candida and Candidiasis – Recent Taxonomic Developments, Invasion Biology, and Novel Active Compounds

“…They showed that diallyl disulphide-loaded niosomes complex decreased the fungal cells and increased the life of cell tissue in contrast to the free formulation. Pałkowski et al [100] investigated the structure-activity relationship of gemini imidazolium compounds using the chemical structure and surface-active properties and antifungal activity against C. albicans ATCC 90028 strain. They remarked that antifungal activity depends not only on the surface-active properties of the compound but also on the substituent type and the position at the chloride moiety of substituents.…”