Optimization of synthesis, antioxidant and enzyme inhibition activities of some β-amino carbonyl derivatives using experimental design

In this study, β-amino carbonyl derivatives were synthesized via the Mannich reaction, and their antioxidant and enzyme inhibition activities were comprehensively evaluated. Initially, the reaction conditions were statistically optimized to maximize yield, with the highest yield (72%) obtained using 1 mL of lemon juice as a catalyst and ethanol as the solvent. Following optimization, ten different β-amino ketone derivatives were synthesized using a 1:1:1 molar ratio of aldehyde, amine, and ketone. Structural characterization was performed using IR, NMR, and mass spectrometry (MS) analyses, confirming the structures of the synthesized compounds. Notably, compound 4g exhibited a predominant anti isomer ratio based on NMR data. Antioxidant activities were assessed using both the DPPH and CUPRAC methods. Compound 4g showed the highest antioxidant capacity in the CUPRAC assay, while compound 4e demonstrated the strongest free radical scavenging activity in the DPPH test. Enzyme inhibition studies were conducted to evaluate the inhibitory effects of the synthesized compounds on hCA I, hCA II, and acetylcholinesterase (AChE) enzymes. Compounds 4a and 4h exhibited potent inhibitory activity against both hCA I and hCA II isoenzymes. Moreover, compounds 4a, 4d, and 4j showed acetylcholinesterase inhibition comparable to the reference inhibitor tacrine. Particularly, 4a and 4h were highlighted for their multi-target enzyme inhibition potential. In conclusion, the synthesized Mannich base derivatives demonstrated promising antioxidant properties and significant enzyme inhibition potential, suggesting their possible application as therapeutic agents in pharmaceutical research.