1 Aromatic selenocyanates as a new class of non - mutagenic 2 antimicrobial selenium compounds with pronounced activity against 3 multidrug resistant ESKAPE bacteria 4

Selenocyanates form an interesting class of organic selenium compounds as they serve as 21 multifunctional agents (being the precursors of seleninic acids and diselenides in synthetic 22 chemistry and as antimicrobial and cytotoxic agent in biology) and, due to their similarity with 23 better known thiocyanates promise high biological activity. Yet whilst selenocyanates are common 24 in synthetic chemistry, they are rarely considered in pharmaceutical design. Arylmethyl 25 selenocyanates (1-13) have been synthesized and an insight into their structural properties using 26 X-ray crystallography has been obtained. The compounds subsequently have been evaluated for 27 their potential antimicrobial, nematicidal and cytotoxic activity. ADMET properties in vitro, using 28 mutagenicity (AMES) and permeability (PAMPA) tests, have been determined. The compounds 29 exhibit pronounced activity against various strains of bacteria (both Gram-positive and 30 Gram-negative) and yeasts. Among them, benzylselenocyanate (1) represents the most active 31 anti-ESKAPE agent, with potent antibacterial activity, especially against multidrug resistant MRSA 32 strains (HEMSA 5). Our results demonstrate that the arylmethyl selenocyantes are not only 33 non-mutagenic but also possess moderate cytotoxic activity against cancer cells. 34