Discussion of antimicrobial and antifungal activity of 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol

Abstract

Studying new biologically active substances nowadays become increasingly important. The current range of the pharmaceutical market requires constant updating of domestic products. The main requirements for new medications are high efficiency and low toxicity. Aim. Modern pharmaceutical science separates 1,2,4-triazole derivatives as a significant class to create new biologically active compounds. Our purpose is to find novel derivatives of 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol, to study their antimicrobial and antifungal activity. Objects of research are derivatives of 4-amino-5-methyl-4H-1,2,4-triazole-3-thiol. Methods and results. The sensitivity of the microorganisms to the new synthesized compounds was determined by serial dilutions method in accordance with the “methodological guidelines” at the Department of Microbiology, Virology and Immunology (Zaporіzhzhia State Medical University). During initial studies with drug concentrations of 1 mg / ml, a series of two-fold serial dilutions of drug in the Mueller-Hinton solution in a volume of 1 ml were prepared, and then a microbial suspension was added to each tube in amount of 0.1 ml (106 microbial cells/ml). Reference test culture of Gram-positive and Gram-negative bacteria was used for primary screening studies of synthesized substances. As a set of standard test strains we took Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Candida albicans ATCC 885–653. All test strains have been obtained from the bacteriological laboratory of the State institution “Zaporizhzhіa Regional Laboratory Center of the State Sanitary and Epidemiological Service of Ukraine”. As a control of the antimicrobial activity of compounds we used 0.05 % chlorhexidine “Fargomed”. Total results of antifungal and antimicrobial activity. The results showed that the leader compound is 4-((4-brombenzyliden)amino)-5-methyl-4H-1,2,4-triazole-3-thiol, which showed antifungal and antimicrobial activity against Candida albicans MIC – 7,8–62.5 ug/ml, MBtsK – 15.6–250 ug/ml. Recovery of this compound, namely transition to 4-((4-bromobenzyl)amino)-5-methyl-4H-1,2,4-triazole-3-thiol, has no antifungal activity, but demonstrates antimicrobial activity against Staphylococcus aureus. Conclusions. Researches have established some “structure–effect” relationship, and also found the compound, the antifungal activity of which is higher than in the reference chlorhexidine preparation.