Abstract
AIM: The purpose is to synthesize a new class of furan-based chalcone compounds (KD1-KD14) and to investigate their monoamine oxidase (MAO)-A and -B inhibitory activities. MATERIAL AND METHOD: The 14 chalcones were synthesized using an open mortar and pestle. Lead molecules were screened via inhibitory activity, BBB permeability, and computation studies. RESULTS: Most of the tested compounds showed promising activity for MAO-B over than MAO-A. Among the molecules, KD1 and KD9 revealed the significant inhibitory potentials toward MAO-B with IC(50) values of 0.023 ± 0.004 and 0.015 ± 0.001 µM, respectively, and with high selectivity indices of 723.04 and >2666.66, respectively, over MAO-A. Further, kinetics and reversibility test revealed that both KD1 and KD9 were competitive reversible MAO-B inhibitors with K(i) values of 13.5 ± 4.95 and 6.15 ± 0.92 nM, respectively. Additionally, the PAMPA test showed that both KD1 and KD9 compounds permeated the central nervous system. Furthermore, molecular docking and dynamics simulations showed that both the chemicals formed pi-cation and hydrogen bonds with the MAO-B pocket and stabilized the MAO-B over the course of a 100 ns simulation. CONCLUSION: Our results revealed that KD1 and KD9 are potent selective, reversible, and competitive MAO-B inhibitors.