ABSTRACT
The tetra-para-guanidinoethyl-calix[4]arene, its distally-disubstituted ether derivatives involving 2,2'-bithiazolyl- or 2,2'-bipyridyl-methyl groups, as well as the para-guanidinoethylphenol and its analogous derivatives have been synthesized, fully characterized and evaluated as antibacterial agents towards both gram positive and gram negative reference bacteria. The simple phenolic species showed lower activity than their calixarene analogues, confirming the hypothesis that a synergistic effect should result from the spatial organization of guanidinium and heterocycles on a macrocyclic scaffold. Introduction of the bithiazole and bipyridine substituents enhanced the activity of simple phenol derivatives, reaching, for the two Staphylococcus aureus strains in particular, the values obtained for their calixarenic parents. MTT viability assays were carried out to determine selectivity indexes.
Subject(s)
Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Guanidines/chemical synthesis , Anti-Bacterial Agents/chemistry , Bacteria/growth & development , Benzamidines/chemical synthesis , Benzamidines/chemistry , Benzamidines/pharmacology , Cell Survival/drug effects , Cells, Cultured , Fibroblasts/cytology , Fibroblasts/drug effects , Guanidines/chemistry , Guanidines/pharmacology , Humans , Microbial Sensitivity Tests , Phenol/chemistry , Staphylococcus aureus/drug effects , Staphylococcus aureus/growth & developmentABSTRACT
A water-soluble calixarene-based heterocyclic podand incorporating a quinolone antibiotic subunit, the nalidixic acid, was synthesised and fully characterised. Its prodrug behaviour was assessed in vitro by HPLC, demonstrating the release of the tethered quinolone in model biological conditions. Microbiological studies performed on various Gram-positive and Gram-negative reference strains showed very interesting antibacterial activities.