Selenocyanates form an interesting class of organic selenium compounds as they serve as multifunctional agents (being the precursors of seleninic acids and diselenides in synthetic chemistry and as antimicrobial and cytotoxic agent in biology) and, due to their similarity with better known thiocyanates promise high biological activity. Yet whilst selenocyanates are common in synthetic chemistry, they are rarely considered in pharmaceutical design. Arylmethyl selenocyanates (1-13) have been synthesized and an insight into their structural properties using X-ray crystallography has been obtained. The compounds subsequently have been evaluated for their potential antimicrobial, nematicidal and cytotoxic activity. ADMET properties in vitro, using mutagenicity (AMES) and permeability (PAMPA) tests, have been determined. The compounds exhibit pronounced activity against various strains of bacteria (both Gram-positive and Gram-negative) and yeasts. Among them, benzylselenocyanate (1) represents the most active anti-ESKAPE agent, with potent antibacterial activity, especially against multidrug resistant MRSA strains (HEMSA 5). Our results demonstrate that the arylmethyl selenocyantes are not only non-mutagenic but also possess moderate cytotoxic activity against cancer cells.

Currently, studies are being conducted on the possible role of the cytoprotective effect of biologically active substances in conditions of cerebral hypoxia or cardiomyopathies. At the same time, oxidative stress is considered as one of the important mechanisms of cellular cytotoxicity and a target for the action of cytoprotectors. The aim of this study is to search for derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones. The probability of cytoprotective action was assessed by two tests by measuring cell viability (with neutral red dye and MTT test). It was found that some derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones under the conditions of our experiment have a pronounced cytoprotective activity, providing better cell survival in vitro, including the MTT test and conditions of blood hyperviscosity. To correlate the obtained results in vitro, molecular docking of the synthesized derivatives was also carried out. The standard drug omeprazole (co-crystallized with the enzyme) was used as a standard. It was shown that all synthesized derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones had higher affinity for the selected protein than the standard gastro-cytoprotector omeprazole. The studied derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones also fully satisfy Lipinski's rule of thumb of five (RO5), which increases their chances for possible use as orally active drugs with a good ability to absorption and moderate lipophilicity. Thus, the results obtained make it possible to evaluate derivatives of 3-(arylmethyl)-6-methyl-4-phenylpyridin-2(1H)-ones as having a relatively high cytoprotective potential.