Аңдатпа
Beta-carboline alkaloids show a wide range of psychopharmacological effects (for example, some beta-carboline alkaloids facilitate dopaminergic transmission and interact with dopaminergic receptors D1 and D2 in the striatum). This article presents data on neuroprotective effects of alkaloid compounds using computer simulation methods, docking-based virtual screening, and experimental pharmacology. The purpose of the study was to investigate the neuroprotective/stress-protective action of new derivatives of alkaloid compounds using the methods of computer simulation, docking-based virtual screening, and experimental pharmacology. Through ChemDraw, MGLTools programs, they have used computer modeling of the molecules of alkaloid derivatives, docking-based virtual screening, DRD2 receptor, and three-dimensional models of the ligand molecules. The binding energy of an individual conformation was used as a final result, which shows the strength of the interaction between the ligand and the target molecule. 22 compounds of alkaloids and their derivatives were studied. Virtual molecule modeling was performed for compounds and receptors, “ligand-target” molecule docking was carried out, and candidate compounds were selected. In vivo experimental studies of the neuroprotective effects of these compounds were conducted in the emotional stress model. The effects of harmine, norharmane, and guanine alkaloids on immobility time in the forced swimming test in mice, a model of depression in animals, were studied. A forced swimming test and an elevated plus-maze were used to determine the antidepressant and anxiolytic effects of harmine in rats. According to the docking results, the presented molecules of alkaloid compounds showed interactions with dopamine receptorD2. The results obtained in the “Elevated Plus Maze” test showed that the animals treated with 9-methoxy-2-phenyl-11H-indolisino[8,7-β]indole, lappaconitine and cytisine at a dose of 5 mg/kg, compared to rats in the control group, experienced an anxiolytic (anti-anxiety) actionin the experimental emotional stress.