CHALCONE ANALOGUES AS POTENTIAL MEDICINES OF PATHOGENETIC THERAPY OF ALZHEIMER'S DISEASE: IN VITRO SCREENING

Abstract

Introduction. Alzheimer's disease is one of the most common forms of dementia, the pathogenesis of which is based on the accumulation of β–amyloid plaques in brain structures and the development of cholinergic deficiency. The aim of the study was to evaluate the effect of chalcone analogues on the change in acetylcholinesterase activity and the process of β-amyloid aggregation in vitro. Material and methods. The tested compounds were six bis-substituted chalcone analogues, which were dissolved in dimethylsulfoxide during the analysis to obtain double dilutions. The effect of the studied substances on the activity of acetylcholinesterase was evaluated by the modified Ellman method. The change in the aggregation process of β-amyloid particles was determined in reaction with congo red after 3, 6 and 9 days of incubation. Based on the obtained results of the «% inhibition- concentration» relationships, the IC50 index was calculated, which was expressed in mmol/ml. Results. In the course of the study, it was shown that the analyzed chalcone analogues inhibit the aggregation of β-amyloid particles starting from the 6th day of incubation with a maximum on the 9th day. At the same time, the compounds that showed the highest level of activity were trimethoxy-substituted substances under the codes AZBAX4 and AZBAX6, whose IC50 on the 9th day of the study was 21.4±0.928 mmol/ml and 32.4±0.456 mmol/ml, respectively. Also, a high level of anticholinesterase properties was established for these compounds with IC50 of 35.9±0.991mmol/ml and 25.1±0.261 mmol/ml, respectively. The rest of the tested compounds showed a lower level of activity. Conclusion. The study showed that chalcone analogues under the codes AZBAX4 and AZBAX6 inhibit the activity of acetylcholinesterase and the pro-cess of aggregation of β-amyloid in vitro, which makes these compounds promising for further study in order to develop medicines for the pathogenet-ic treatment of Alzheimer's disease.