title: 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.
authors.affiliation: Department of Pharmaceutical Technology, Nicolaus Copernicus University, Jurasza 2, 85-094 Bydgoszcz, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Pałkowski
authors.affiliation: Institute of Computing Science, Poznań University of Technology, Piotrowo 2, 60-965 Poznań, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Błaszczyński
authors.affiliation: Institute of Chemical Technology, Poznań University of Technology, Skłodowskiej-Curie 2, 60-965 Poznań, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Skrzypczak
authors.affiliation: Institute of Chemical Technology, Poznań University of Technology, Skłodowskiej-Curie 2, 60-965 Poznań, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Błaszczak
authors.affiliation: Department of Organic Chemistry, Nicolaus Copernicus University, Jurasza 2, 85-094 Bydgoszcz, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Nowaczyk
authors.affiliation: Department of Microbiology, Nicolaus Copernicus University, Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wróblewska
authors.affiliation: Department of Microbiology, Nicolaus Copernicus University, Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Kożuszko
authors.affiliation: Department of Microbiology, Nicolaus Copernicus University, Skłodowskiej-Curie 9, 85-094 Bydgoszcz, Poland.
authors.forename: Eugenia
authors.initials: E
authors.lastname: Gospodarek
authors.affiliation: Institute of Computing Science, Poznań University of Technology, Piotrowo 2, 60-965 Poznań, Poland ; Systems Research Institute, Polish Academy of Sciences, Newelska 6, 01-447 Warsaw, Poland.
authors.forename: Roman
authors.initials: R
authors.lastname: Słowiński
authors.affiliation: Department of Pharmaceutical Technology, Nicolaus Copernicus University, Jurasza 2, 85-094 Bydgoszcz, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Krysiński
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects / Q000472:pathogenicity; D002177:Candidiasis / Q000188:drug therapy* / Q000382:microbiology; D025141:Drug Resistance, Fungal / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C411462:1,25-dihydroxy-21-(3-hydroxy-3-methylbutyl)vitamin D(3); D000935:Antifungal Agents; D007093:Imidazoles; C029899:imidazole; D002117:Calcitriol