Investigation of monoamine oxidase inhibitory activities of new chalcone derivatives

Abstract

Purpose: In the present study, it is aimed to investigate monoamine oxidase (MAO) enzyme inhibition potencies of some new chalcone derivatives. Materials and Methods: Nine novel chalcone derivatives were synthesized and structures of the synthesized compounds (2a-2i) were confirmed by spectroscopic methods. Inhibitory activities of the compounds against MAO-A and MAO-B enzymes have been determined via in-vitro fluorometric method. Effects of the compounds on substrate level were measured by an LC-MS/MS method. Enzyme kinetics studies were carried out for the most active compound 2i using Lineweaver-Burk plots. Results: Compounds 2c, 2e and 2i displayed notable inhibition against hMAO-B with lower IC50 values than 1 mu M. The most active compound 2i displayed significant inhibition by IC50 of 0.13 mu M. Results of substrate level quantification study were in an agreement with fluorometric enzyme inhibition assay. Competitive type of inhibition was determined for compound 2i as a result of enzyme kinetic studies. Conclusion: Synthesized compounds displayed more selectivity towards hMAO-B. In this study, the results of inhibitor effects of compounds 2c, 2f and 2i are promising for the synthesis of similar derivatives with enhanced MAO inhibitory activity and therefore for the development of new molecules which may be drug candidates against Parkinson's disease.