Synthesis of Some Novel (Z)-3-ethylidene-5,7-dimethylthiochroman- 4-one Derivatives and Study of its Monoamine Oxidases Inhibitory Activity

Abstract

Background: Chroman-4-one, also known as 2,3-dihydro-1-benzopyran- 4-one, is a heterocyclic compound with a benzene nucleus fused to a 2,3-dihydro-g-pyranone ring. The synthesis of chroman-4-one derivatives is a very appealing aspect in the field of natural and medicinal chemistry.Materials and Methods: The (Z)-3-ethylidene-5,7-dimethylthiochroman- 4-one derivatives were, synthesized and evaluated intended for their Monoamine oxidases (MAO)-A and MAO-B inhibitory activity using in vitro fluorometric technique. The majority of synthetic process to acquire(Z)-3-ethylidene-5,7-dimethylthiochroman-4-one derivatives engage condensation catalyzed by acid or base of a range of derivatives of 5,7-dimethylchroman-4-one and 4,6-dimethylbenzofuran-3(2H)-one with the benzaldehyde. The Z-isomers that resulted were usually obtained by photoisomerization of the synthesized E-isomers. Synthesized molecules structures (S-1 to S-18) were established by IR, NMR, mass and elemental analysis.Results: The in vitro activity of synthesized (Z)-3-ethylidene-5,7- dimethylthiochroman-4-one derivatives against MAO isoform displayed selectivity in the direction of MAO B isoform. The synthesized derivatives S11 of (Z)-3-ethylidene-5,7-dimethylthiochroman-4-one displayed 7.32 μM (IC50) against MAO-B.Conclusion: Weak to moderate electron pumping and withdrawing groups favor selectivity for hMAO-B, whereas strong deactivators render them non-selective for isoforms. Mono-substitution of methoxy groups at the o- and m-positions improves potency while bi-substitution improves potency and selectivity. The active compounds’ ADME predictions revealed that these synthesized compounds may possess drug likeliness confirmed by excellent pharmacokinetic profiles.

Keywords: Chromanone; Chalcones; Schiff base; hMAO inhibitory activity; dimethylthiochroman-4-one