Design, Synthesis, and Biological Evaluations of Novel Naphthalene-based Organoselenocyanates

Abstract

Organoselenocyanates are an interesting category of organoselenium compounds as they usually warrant potential biological activity and give access to other selenium (Se) reactive species, such as selenides diselenides, selenols, and seleninic acids. Twenty-three naphthalene-based organoselenocyanates were synthesized and assessed for their potential anticancer and antimicrobial activities. Among the synthesized compounds, 4,4'-diselanediylbis(naphthalen-1-amine) (3), 5-imino-4-((4-selenocyanatonaphthalen-1-yl)diazenyl)-4,5-dihydro-1H-pyrazol-3-amine (5a), 5-amino-4-((4-selenocyanatonaphthalen-1-yl)diazenyl)-2,4-dihydro-3H-pyrazol-3-one (5b) demonstrated pronounced anti-cancer activity against the breast cancer (MCF-7) cells with minimal cytotoxicity to the primary fibroblasts (WI-38). Moreover, 5-imino-4-((4-selenocyanatonaphthalen-1-yl)diazenyl)-4,5-dihydro-1H-pyrazol-3-amine (5a) and 2-(naphthalen-2-yloxy)-N-(4-selenocyanatonaphthalen-1-yl)acetamide (8) exhibited a comparable cytotoxicity to adrucil (5-FU) and showed an interesting therapeutic index (TI) (e.g., 15 and 12, respectively). Fortunately, 4,4'-diselanediylbis(naphthalen-1-amine) (3), 5-imino-4-((4-selenocyanatonaphthalen-1-yl)diazenyl)-4,5-dihydro-1H-pyrazol-3-amine (5a), 5-amino-4-((4-selenocyanatonaphthalen-1-yl)diazenyl)-2,4-dihydro-3H-pyrazol-3-one (5b) manifested also potential antimicrobial properties against Escherichia coli bacteria and Candida albicans yeast. Our results point to selective cytotoxicity against MCF-7 cells and good antimicrobial activity for some of the synthesized naphthalene-based organoselenocyanates and therefore considered potential drug candidates.