Synthesis and Molecular Docking Studies of (E)-4-(Substituted-benzylideneamino)-2H-Chromen-2-one Derivatives: Entry to New Carbonic Anhydrase Class Of Inhibitors

Abstract

The present article illustrated the synthesis and characterization of a novel series of (E)-4-(substituted-benzylideneamino)-2H-chromen-2-one derivatives 4a-4j in good to excellent yields. The target compounds were synthesized by refluxing 4-aminocoumarin with aromatic aldehydes in ethanol. The structural confirmation was achieved by spectroscopic techniques such as (¹H, ¹³C-NMR and FT-IR) and elemental analysis. The synthesized compounds were evaluated for carbonic anhydrase II (CA-II) inhibition and free radical scavenging activity. All the compounds showed CA-II inhibition in the micro molar range. The compound 4c exhibited higher potential in the series with IC₅₀=0.0928±0.00545 µM (standard Acetazolamide IC₅₀=0.997±0.0586 µM). Pharmacological investigations showed that the synthesized compounds 4a-4j obey Lipinsk’s rule. Compound 4c elicited drug likeness and showed drug score value of 0.05. Molecular docking analysis showed that compound 4c interacts with Asn66 and Gln91 amino acid residues. [Graphical Abstract].

Graphical Abstract

Key words

Chromen derivatives - Schiff bases - Carbonic anhydrase-II inhibition - Antioxidant activity - Rule of five - Binding analysis

• References

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