title: New ethacridine derivatives as the potential antifungal and antibacterial preparations.
abstract: Until the 20th century fungal infections were rather easy cured, and the need of new antifungal drugs was low. However, low choice of antifungal preparations, their toxicity, limited spectrum of action, and ability to produce resistant strains show the need of new effective medicines for systemic fungal diseases in nowadays. Our goal of research was to synthesize new antimicrobial compounds containing three or more pharmacophores in one molecule. The initial 5-substituted-2-methylmercaptothiazolidin-4-ones were subjected to S-demethylation to yield 2-amino-substituted thiazolidinones. Ethacridine, nitrofuran aldehydes and nitrobenzene aldehyde as pharmacophoric amino or aldehyde group having compounds have been used. Antimicrobial (antifungal) activity of the new compounds was screened in vitro in these bacterial cultures: Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633, Klebsiella pneumoniae ATCC 33499 and fungal cultures: Candida albicans ATCC 60193, Candida glabrata, Candida krusei, Candida kefyr ATCC 8614, Candida tropicalis ATCC 8302, Candida parapsilosis. Results showed that the new compounds were significantly more effective as antimicrobial agents than initial preparation ethacridine. Ethacridine derivatives were not only effective against numerous gram-positive and some gram-negative bacteria, but the spectrum of action has been discovered against fungi. Minimal fungistatic concentration varies in the range 10.0-750 microg/mL and antibacterial concentration is in the range 62.5-1000 microg/mL. Compound 2a having nitrofuryl substituent in the fifth position of tiazolidine cycle was the most active of synthesized ethacridine compounds. The obtained results gave the opportunity to separate the perspective group of potential antiinfective compounds.
authors: Department of Pharmaceutical Chemistry and Pharmacognosy, Kaunas University of Medicine, Kaunas, Lithuania. Vilma.Petrikaite@med.kmu.lt
authors: Vilma
authors: V
authors: Petrikaite
authors: Eduardas
authors: E
authors: Tarasevicius
authors: Alvydas
authors: A
authors: Pavilonis
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000891:Anti-Infective Agents, Local / Q000494:pharmacology; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects; D003470:Culture Media; D004975:Ethacridine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D005658:Fungi / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D008826:Microbial Sensitivity Tests; D008828:Microbiological Techniques; D009581:Nitrofurans / Q000138:chemical synthesis*; D053778:Thiazolidines / Q000138:chemical synthesis*
chemical_list: D000900:Anti-Bacterial Agents; D000891:Anti-Infective Agents, Local; D000935:Antifungal Agents; D003470:Culture Media; D009581:Nitrofurans; D053778:Thiazolidines; D004975:Ethacridine