rhodanine and Staphylococcal-Infections

Three series of 5-aryl-1,2,4-triazole-3-thione derivatives containing a rhodanine moiety (5a-k, 6a-i, and 7a-i) have been synthesized, characterized and evaluated for their antibacterial activity. Some of these displayed potent antibacterial activity against several Gram-positive and Gram-negative bacterial strains (including multidrug-resistant clinical isolates) with minimum inhibitory concentration (MIC) values in the range of 4-64 μg/mL and minimum bactericidal concentration (MBC) values in the range of 8-256 μg/mL. Compared with previously reported rhodanine derivatives, these compounds exhibited a broad spectrum of antibacterial activity by means of introducing 4-amino-5-aryl-1,2,4-triazole-3-thione moiety. Notably, compound 5f exhibited good antibacterial activity against Staphylococcus aureus RN 4220, S. aureus 209, S. aureus 503, Gram-negative bacteria (Escherichia coli 1924), and Candida albicans 7535 with MBC values of 8 or 16 μg/ml. All of the compounds synthesized in the current Letter were characterized by (1)H NMR, (13)C NMR, infrared and mass spectroscopy.

Topics: Anti-Infective Agents; Candida albicans; Candidiasis; Escherichia coli; Escherichia coli Infections; Humans; Rhodanine; Staphylococcal Infections; Staphylococcus aureus; Thiones; Triazoles

Here, we describe the most promising small synthetic organic compounds that act as potent Sortase A inhibitors and cater the potential to be developed as antivirulence drugs. Sortase A is a polypeptide of 206 amino acids, which catalyzes two sequential reactions: (i) thioesterification and (ii) transpeptidation. Sortase A is involved in the process of bacterial adhesion by anchoring LPXTG-containing proteins to lipid II. Sortase A inhibitors do not affect bacterial growth, but they restrain the virulence of pathogenic bacterial strains, thereby preventing infections caused by Staphylococcus aureus or other Gram-positive bacteria. The efficacy of the most promising inhibitors needs to be comprehensively evaluated in in vivo models of infection, in order to select compounds eligible for the treatment of bacterial infections in humans.

Topics: Adamantane; Aminoacyltransferases; Animals; Anti-Bacterial Agents; Bacterial Adhesion; Bacterial Proteins; Benzoates; Carbolines; Cysteine Endopeptidases; Enzyme Inhibitors; Humans; Models, Molecular; Nitriles; Protein Conformation; Rhodanine; Small Molecule Libraries; Staphylococcal Infections; Staphylococcus aureus; Thiazoles; Thiones