Synthesis of Mannich Bases by Two Different Methods and Evaluation of their Acetylcholine Esterase and Carbonic Anhydrase Inhibitory Activities

Background: Mannich bases are an important compounds in medicinal chemistry. They have wide range of biological activities including carbonic anhydrase (CA) inhibitory and acetylcholine esterase inhibitory (AChE) activities. Objective: It was aimed to synthesize Mannich bases, 1-aryl-3-(morpholin-4-yl/piperidin-1-yl)-1propanone hydrochloride, by microwave irradiation and conventional heating methods to compare the methods in terms of reaction times and yields and to investigate their inhibitory effects on AChE enzyme and CA isoenzymes. Method: Mannich bases were synthesized using conventional heating and microwave irradiation methods under different reaction conditions. Inhibitory effects of the compounds on CA isoenzymes and AChE were evaluated according to literature procedure. Results: IC50 and Ki values of the compounds were evaluated against hCA I, II and AChE. The compounds had more potent or equal Ki values with the references used. Conclusion: This study makes an important contribution to the Mannich base library in terms of synthetic strategy. According to IC50 or Ki values the compounds 6 in Series A with morpholine and and 15 in Series B with piperidine towards both hCA I and/or II isoenzymes and the compounds 4 in Series A and 11, 13, 14, 15, 16, and 18 in Series B towards AChE seemed the leader compounds of the study.