1-[4-(morpholin-4-yl)phenyl]-5-phenylpenta-2,4-dien-1-one as a new potent and selective monoamine oxidase-B inhibitor with extended conjugation in chalcone framework.

In this study, 1-[4-(morpholin-4-yl)phenyl]-5-phenylpenta-2,4-dien-1-one ( MO10 ) was prepared by the condensation of 4'-morpholinoacetophenone and cinnamaldehyde in the presence of basic alcoholic medium . The title compound MO10 was assessed for inhibitory activities against two human MAO isoforms, i.e., MAO-A and MAO-B. Interestingly, MO10 showed a remarkable inhibition against MAO-B with an IC 50 value of 0.044 µM along with a selectivity index of 366.13. The IC 50 value was better than that of lazabemide (IC 50 value of 0.063 µM), used as a reference. Kinetics studies revealed that MO10 acted as a competitive inhibitor for MAO-B, with a K i value of 0.0080 µM. In reversibility experiments, MO10 was found to be a reversible inhibitor by observations of inhibition recoveries of MAO-B, comparing to the reference levels. MTT assays showed that MO10 was non-toxic to normal VERO cells with an IC 50 value of 195.44 µg/mL. Molecular docking simulations showed that MO10 properly entered the aromatic cage formed by Y435, Y398 and FAD of MAO-B. On the basis of these results, MO10 can be considered a promising starting compound in development of agents for the treatment of various neurodegenerative disorders. PMID: 32583952 [PubMed - as supplied by publisher]
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research