International Journal of Pharmaceutical Investigation, 2022, 12, 4, 449-454.
DOI: 10.5530/ijpi.2022.4.77
Published: October 2022
Type: Original Article
Authors:
Somesh Kumar Saxena
Department of Pharmaceutical Chemistry, Patel College of Pharmacy, Madhyanchal Professional University, Bhopal, Madhya Pradesh, INDIA.
Om Prakash Agrawal
Department of Pharmaceutical Chemistry, Patel College of Pharmacy, Madhyanchal Professional University, Bhopal, Madhya Pradesh, INDIA.
Ashish Pathak
Department of Pharmaceutical Chemistry, Ravishankar College of Pharmacy, Bhopal, Madhya Pradesh, INDIA.
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.