Guanidinium aryl(oxy)(sulfanyl)(sulfonyl)acetates. Synthesis, structure, and analysis of biological activity
摘要
The reaction of arylchalcogenylacetic acids 1a–e and guanidinium carbonate 2 afforded a series of guanidinium arylchalcogenylacetates 3a–e of the general formula ArXCH2COO− • H2+N=C(NH2)2, where X = O, S, SO2 or absent. The structure of the synthesized compounds was established using IR spectroscopy and 1H and 13C NMR spectroscopy. In silico calculations indicated that salts 3a–e have synthetic and biological availability, drug similarity, can effectively (up to 89%) inhibit the activity of some enzymes, do not have immuno-, cytotoxicity and mutagenicity (probability up to 99%), and are virtually harmless (LD50 500 mg kg−1). The effect of salts 3a–e on the growth of a number of pathogenic bacteria (Listeria monocytogenes, Staphylococcus aureus, Yersinia enterocolitica, Yersinia pseudotuberculosis, Yersinia pestis, and Vibrio cholerae) was studied in vitro. At high concentrations, salts 3a–e exhibited a moderate inhibitory effect (up to 40–50%) on the growth of microorganisms, while at low concentrations they exhibited significant stimulating activity (up to 82%). The activity of salts 3a–e was found to depend on their structure and composition: the highest activity was observed for ArX = 4-ClC6H4S, 4-ClC6H4SO2, and indol-3-ylsulfanyl. The sulfur-containing compounds improved the specific activity of nutrient media, in particular, increasing the germination rate of test bacteria (up to ∼ 200%).