Synthesis, Antioxidant Evaluation, and Docking Simulation of New Mannich-Type β-Amino Ketone

Given the biological significance of β-amino ketone compounds and the synthetic challenges in obtaining enantiomerically pure forms, a new series of Mannich-type β-amino ketone derivatives was successfully synthesized, with exclusive formation of the anti-enantiomer. These compounds were fully characterized and extensively evaluated for their biological activities. Antioxidant properties were assessed using the DPPH radical scavenging assay, and the results demonstrated excellent antioxidant activity for the synthesized molecules.

In addition, molecular docking simulations were conducted to investigate the interaction of the compounds with key biological targets, particularly acetylcholinesterase and tubulin. The anti-enantiomers exhibited strong binding affinities, suggesting potential anti-Alzheimer’s and anticancer activities. The docking analysis revealed multiple hydrogen bonding and hydrophobic interactions with critical amino acid residues in the active sites, supporting their strong inhibitory potential.

Furthermore, ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling showed that the compounds possess favorable drug-likeness properties. Specifically, they were predicted to cross the blood–brain barrier and to comply with Lipinski’s Rule of Five, indicating potential oral bioavailability and activity within the central nervous system.

In conclusion, these newly synthesized Mannich-type β-amino ketone derivatives exhibit promising pharmacological profiles and represent valuable candidates for further development as therapeutic agents targeting oxidative stress, neurodegenerative diseases, and cancer. The synthesized anti-β-amino ketone derivatives show great potential as lead compounds for future drug development.