The problem of antimicrobial resistance is an important global public health challenge. We propose that a development of new antibiotic compounds around known natural substances is a solution to this problem. We investigate reengineer natural products into potent antibiotics. Uracil fragment is abundant in nature and significant to treat infectious diseases due to its affection to the replication of the bacterial chromosome. 12 new uracil S-derivatives were obtained and tested for their in vitro antimicrobial properties. N3 -(thietan-3-yl)- and N3 -(1,1-dioxothietan-3-yl)uracils derivatives were synthesized by thietanylation of 6-methyluracil with 2-chloromethylthiirane and subsequent oxidation of the thietan ring. A method of their alkylation with ethyl-2-chloroacetate was developed and acetohydrazides containing 3-(thietan-3-yl)- and 3-(1,1-dioxothietan-3-yl)uracilyls fragments in the acetyl group were obtained by hydrazinolysis of 2-(thietanyluracil-1-yl)acetic acid ethyl esters. Their interaction with β-dicarbonyl compounds, anhydride of mono- and dicarboxylic acids was studied. Antimicrobial activity was determined by the agar diffusion method on test organisms: S. aureus, E. coli, P. vulgaris, K. pneumoniae, C. diversus, E. aerogenes, P. aeruginosa, S. abosit. N-acyl-5-hydroxypyrazolines and N,N'-diacylhydrazines of 6-methyluracil thietanyl- and dioxothietanyl derivatives showed high antimicrobial activity, which is consistent with the results of structure activity relationship analysis (MIC 0.1-10 μg/ml).
Keywords: antibacterial and antifungal activities; pyrimidine; thietan.
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