Inhibition of Monoamine Oxidases by Functionalized Coumarin Derivatives:  Biological Activities, QSARs, and 3D-QSARs

Abstract

A large series of coumarin derivatives (71 compounds) were tested for their monoamine oxidase A and B (MAO-A and MAO-B) inhibitory activity. Most of the compounds acted preferentially on MAO-B with IC(50) values in the micromolar to low-nanomolar range; high inhibitory activities toward MAO-A were also measured for sulfonic acid esters. The most active compound was 7-[(3, 4-difluorobenzyl)oxy]-3,4-dimethylcoumarin, with an IC(50) value toward MAO-B of 1.14 nM. A QSAR study of 7-X-benzyloxy meta-substituted 3,4-dimethylcoumarin derivatives acting on MAO-B yielded good statistical results (q(2)() = 0.72, r(2)() = 0.86), revealing the importance of lipophilic interactions in modulating the inhibition and excluding any dependence on electronic properties. CoMFA was performed on two data sets of MAO-A and MAO-B inhibitors. The GOLPE procedure, with variable selection criteria, was applied to improve the predictivity of the models and to facilitate the graphical interpretation of results.

Synthesis of potential dual binding site acetylcholinesterase inhibitors through an efficient solid phase approach based on the Mitsunobu reaction

“…Recently, our group has published the synthesis and the biological activity of a series of 7-substitued coumarin derivatives of general structure I displaying a dual AChE/MAO inhibitory activity ( Figure 1). 13 The inhibitory potency towards the MAO, in particular the MAO-B isoform, was in the nanomolar range, whereas a lower potency, in the micromolar range, was found against AChE. The absence of protonated or quaternary nitrogen atoms in compounds I and the prevalent hydrophobic character of the substituted coumarin moieties, suggested that the inhibitory activity of I could arise from an interaction at the peripheral binding site located at the entrance of the enzymic gorge ending with the primary (anionic) binding site.…”

QSAR Studies of 2-Phenoxyacetamide Analogues, a Novel Class of Potent and Selective Monoamine Oxidase Inhibitors

“…15,16 Establishment of structure-activity relationship helpful in understanding the interaction of the newly designed molecule with MAO enzyme. 17 Some acetamide derivatives with potent MAO inhibiting activity were found among them safinamide was found potent MAO inhibitor.…”

Biosynthesis of Coumarin Glycosides by Transgenic Hairy Roots ofPolygonum multiflorum

“…The chemical structures of all the compounds were elucidated by a comparison of their melting point, 1 H NMR and 13 C NMR, data with literatures. [9][10][11][12][13][14][15] Compounds 13 and 14 were biosynthesized from substrates 4 and 5 under the same process in the literature. 8) Compound 15 was identified by MS and NMR spectra.…”