title: Relationship between aggregation properties and antimicrobial activities of alkylphosphocholines with branched alkyl chains.
abstract: Synthesis of five alkylphosphocholines with branched alkyl chains (Isophol-PCs) with different length of alkyl chains was described. Isophol(8)-PC and Isophol(12)-PC represent new compounds. The physico-chemical properties of Isophol-PCs were determined, critical micelle concentration and types of formed aggregates in aqueous solutions were investigated. The biological activities of Isophol-PCs have been studied for the first time in the present study. Antimicrobial activities of alkylphosphocholines were studied against bacteria (Staphylococcus aureus, Escherichia coli), yeast (Candida albicans) and pathogenic free-living amoebae (Acanthamoeba lugdunensis and Acanthamoeba quina). A. lugdunensis and A. quina are relatively insusceptible to action of miltefosine (standard compound of alkylphosphocholines) and therefore they are good models for studies of amoebicidal action of the investigated compounds. Relationship between structure, physico-chemical and biological activities of Isophol-PCs was discussed. S. aureus and C. albicans were sensitive to action of Isophol(16)-PC, Isophol(20)-PC. E. coli was not sensitive to action of all studied alkylphosphocholines in the concentrations equal to, or less than 10mM. Among all the synthesized compounds, Isophol(16)-PC had the highest level of activity against both strains of Acanthamoeba. The minimum trophocidal concentrations of Isophol(16)-PC against A. lugdunensis and A. quina are about four times lower than the minimum trophocidal concentrations of miltefosine against both strains.
authors.affiliation: Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia. lukac@fpharm.uniba.sk
authors.forename: Miloš
authors.initials: M
authors.lastname: Lukáč
authors.forename: Mária
authors.initials: M
authors.lastname: Garajová
authors.forename: Martin
authors.initials: M
authors.lastname: Mrva
authors.forename: Marián
authors.initials: M
authors.lastname: Bukovský
authors.forename: František
authors.initials: F
authors.lastname: Ondriska
authors.forename: Eszter
authors.initials: E
authors.lastname: Máriássy
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Devínsky
authors.forename: Ivan
authors.initials: I
authors.lastname: Lacko
mesh_terms: D000048:Acanthamoeba / Q000187:drug effects / Q000254:growth & development; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects / Q000254:growth & development; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D008823:Micelles; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010767:Phosphorylcholine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D000890:Anti-Infective Agents; D008823:Micelles; D010767:Phosphorylcholine