Synthesis, molecular docking, and biological activity of 2-vinyl chromones: Toward selective butyrylcholinesterase inhibitors for potential Alzheimer's disease therapeutics.

We investigated the biological activity of a series of substituted chromeno[3,2-c]pyridines, including compounds previously synthesized by our group and novel compounds whose syntheses are reported here. Tandem transformation of their tetrahydropyridine ring under the action of activated alkynes yielding 2-vinylsubstituted chromones was used to prepare nitrogen-containing derivatives of a biologically active chromone system. The inhibitory activity of these chromone derivatives against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carboxylesterase (CaE) was investigated using the methods of enzyme kinetics and molecular docking. Antioxidant (antiradical) activity of the compounds was assessed in the ABTS assay. The results demonstrated that a subset of the studied chromone derivatives selectively inhibit BChE but do not exhibit antiradical activity. In addition, the results of molecular docking effectively explained the observed features in the efficacy, selectivity, and mechanism of BChE inhibition by the chromone derivatives.

Copper coordination compounds with (5Z,5Z')-2,2'-(alkane-α,ω-diyldiselenyl)-bis-5-(2-pyridylmethylene)-3,5-dihydro-4H-imidazol-4-ones. Comparison with sulfur analogue.

A series of new organic ligands (5Z,5Z')-2,2'-(alkane-α,ω-diyldiselenyl)-bis-5-(2-pyridylmethylene)-3,5-dihydro-4H-imidazol-4-ones (L) consisting of two 5-(2-pyridylmethylene)-3,5-dihydro-4H-imidazol-4-one units linked with polymethylene chains of various lengths (n = 2-10, where n is the number of CH2 units) have been synthesized. The reactions of these ligands with CuCl2·2H2O and CuClO4·6H2O gave Cu2+ or Cu1+ containing mono- and binuclear complexes with Cu2LCl x (x = 2-4) or CuL(ClO4) y (y = 1, 2) composition. It was shown that the agents reducing Cu2+ to Cu1+ in the course of complex formation can be both a ligand and an organic solvent in which the reaction is carried out. This fundamentally distinguishes the selenium-containing ligands L from their previously described sulfur analogs, which by themselves are not capable of reducing Cu2+ during complexation under the same conditions. A higher cytotoxicity and reasonable selectivity to cancer cell lines for synthesized complexes of selenium-containing ligands was shown; unlike sulfur analogs, ligands L themselves demonstrate a high cytotoxicity, comparable in some cases to the toxicity of copper-containing complexes.