An Integrated in Silico, in Vitro, and in Vivo Assessment of the Antioxidant and Neuroprotective Profile of Selenocyanate Compounds.

Cyanate-based compounds have received increasing attention due to their neuroprotective and antioxidant properties, which can be further enhanced by the incorporation of selenium, a key element in redox regulation. In this study, five selenocyanate derivatives (1-5), differing by alkyl or aryl groups, were synthesized and systematically evaluated using an integrated in silico, in vitro, and in vivo approach to explore their pharmacological and toxicological potential. Computational analyses included predictions of pharmacokinetic and toxicological parameters (ADME/T), as well as molecular docking studies targeting neurotransmitter-related enzymes, namely acetylcholinesterase (AChE) and monoamine oxidases (MAO-A and B). Antioxidant activity was evaluated using multiple complementary in vitro assays, including DPPH, ABTS, FRAP, GST-like, and SOD-like, as well as cerebral reactive species (RS). Cerebral AChE, MAO-A, and MAO-B activities were also measured in vitro. In vivo experiments involved evaluating acute oral toxicity in female Swiss mice. In silico results indicated favorable ADME/T profiles and affinity of selenocyanates for the target neurochemical enzymes. In vitro assays revealed antioxidant capacity for selenocyanates, particularly for compounds 1, 4, and 5. All compounds inhibited cerebral AChE and MAO isoforms in vitro, with particular emphasis on compounds 2 and 4 as AChE inhibitors. Therefore, compounds 2 and 4 were tested in vivo and showed no acute toxicity at an oral dose of 50 mg/kg; however, at 300 mg/kg, compound 2 showed signs of toxicity, whereas compound 4 remained non-lethal. Taken together, these results highlight organoselenocyanates, especially compound 4, as promising candidates for the development of antioxidant and neuroprotective agents.