Abstract
The goal of this research is to investigate the antimicrobial activity of nineteen previously synthesized 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole derivatives. The compounds were tested against a panel of three Gram-positive and three Gram-negative bacteria, three resistant strains, and six fungi. Minimal inhibitory, bactericidal, and fungicidal concentrations were determined by a microdilution method. All of the compounds showed antibacterial activity that was more potent than both reference drugs, ampicillin and streptomycin, against all bacteria tested. Similarly, they were also more active against resistant bacterial strains. The antifungal activity of the compounds was up to 80-fold higher than ketoconazole and from 3 to 40 times higher than bifonazole, both of which were used as reference drugs. The most active compounds (2, 3, 6, 7, and 19) were tested for their inhibition of P. aeruginosa biofilm formation. Among them, compound 3 showed significantly higher antibiofilm activity and appeared to be equipotent with ampicillin. The prediction of the probable mechanism by docking on antibacterial targets revealed that E. coli MurB is the most suitable enzyme, while docking studies on antifungal targets indicated a probable involvement of CYP51 in the mechanism of antifungal activity. Finally, the toxicity testing in human cells confirmed their low toxicity both in cancerous cell line MCF7 and non-cancerous cell line HK-2.
Highlights
Despite an indisputable contribution of the existing antimicrobial agents to life expectancy, bacterial infections continue to cause serious diseases which lead to mortality in all parts of the world
The purpose of this study is the experimental testing of the antibacterial and antifungal actions of the synthesized compounds, which was conducted in order to identify the most promising antimicrobial agents and determine which activity should be further evaluated in greater detail
Nineteen triazolo-thiadiazole derivatives were evaluated for their activity in inhibiting numerous Gram-positive and Gram-negative bacteria and fungi
Summary
Charalampos Kamoutsis 1 , Maria Fesatidou 2 , Anthi Petrou 2 , Athina Geronikaki 2, * , Vladimir Poroikov 3 , Marija Ivanov 4 , Marina Soković 4 , Ana Ćirić 4 , Alejandro Carazo 5 and Přemysl Mladěnka 5.
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