3-Coumaranone derivatives as inhibitors of monoamine oxidase

Abstract

The present study examines the monoamine oxidase (MAO) inhibitory properties of a series of 20 3-coumaranone [benzofuran-3(2H)-one] derivatives. The 3-coumaranone derivatives are structurally related to series of α-tetralone and 1-indanone derivatives, which have recently been shown to potently inhibit MAO, with selectivity for MAO-B (in preference to the MAO-A isoform). 3-Coumaranones are similarly found to selectively inhibit human MAO-B with half-maximal inhibitory concentration (IC50) values of 0.004–1.05 µM. Nine compounds exhibited IC50<0.05 µM for the inhibition of MAO-B. For the inhibition of human MAO-A, IC50 values ranged from 0.586 to >100 µM, with only one compound possessing an IC50<1 µM. For selected 3-coumaranone derivatives, it is established that MAO-A and MAO-B inhibition are reversible since dialysis of enzyme–inhibitor mixtures almost completely restores enzyme activity. On the basis of the selectivity profiles and potent action, it may be concluded that the 3-coumaranone derivatives are suitable leads for the development of selective MAO-B inhibitors as potential treatment for disorders such as Parkinson’s disease and Alzheimer’s disease.

<p>Reversible Small Molecule Inhibitors of MAO A and MAO B with Anilide Motifs</p>

“…Reagents and solvents for synthesis were purchased from Sigma-Aldrich, VWR Chemicals, Fisher Scientific, Panreac AppliChem, Alfa Aesar and Chemsolute and were used without further purifications (unless stated otherwise). 1 H NMR and 13 C NMR were recorded on a Bruker AMX spectrometer (Bruker, Germany) at 300 and 75 MHz respectively, where either CDCl 3 or DMSOd 6 was used as a solvent. Tetramethylsilane was used as standard and chemical shifts are reported in parts per million (ppm).…”

“…Thin-layer chromatography (TLC) was carried out using pre-coated silica gel 60 with fluorescence indicator at UV 254 nm (Macherey-Nagel, Germany). The structure and purity of each compound were confirmed using 1 H NMR, 13…”

“…Multiple publications identified two aromatic moieties linked by a short bridging element as mutual MAO scaffold. 8,[12][13][14][15][16] Due to their high stability under physiological conditions, amides were used as linkers in our series. Aromatic moieties bearing different substituents were chosen to elucidate electronic and steric effects on the binding affinities towards both MAO isoforms.…”

Deciphering the detailed structure–activity relationship of coumarins as Monoamine oxidase enzyme inhibitors—An updated review

“…A series of 3-coumaranone derivatives were synthesized and evaluated MAO inhibitory potency which shows the structural resemblance with α-tetralone & 1-indanone, an established MAO-B inhibitor (Van Dyk et al, 2015). The 3-coumaranone was substituted with various benzyloxy groups and various substitutions at o, m, and p positions of benzyloxy groups.…”

Design, Synthesis, and Biological Effect Studies of Novel Benzofuran–Thiazolylhydrazone Derivatives as Monoamine Oxidase Inhibitors

“…On the other hand, benzofuran (oxygen heterocycle) is a common structure found in a wide range of biologically active natural and medicinal compounds, and it is thus a crucial pharmacophore. It can be found in a variety of medicinally relevant molecules with biological action, such as MAO inhibitors. − …”