New 2H-chromene-3-carboxamide derivatives: Design, synthesis and use as inhibitors of hMAO

• New coumarins as potential MAO inhibitors were designed and synthesized.
• Compound 4d exhibited selectivity activity toward MAO-B.
• Docking results indicated that residue CYSA 172 was important for binding.

A series new 2H-chromene-3-carboxamide derivatives 4a–4t were synthesized and evaluated as monoamine oxidase A and B (MAO-A and MAO-B) inhibitors. Among them, compound 4d (IC50 = 0.93 μM, IC50 iproniazid = 7.80 μM) showed the most activity and higher MAO-B selectivity (64.5-fold vs. 1-fold) with respect to the MAO-A isoform. The active compound 4d was also docked into the hMAO-B complex structure active site to determine the probable binding model. The results indicated that conserved residue CYSA 172 was important for ligand binding via hydrogen bond interaction, Pi–Pi interaction was found between the benzene-ring of compound 4d and residue ILEA 199.

Novel coumarine derivatives as potential MAO-B selectivity inhibitors were designed and synthesized. Enzymatic assays revealed that compound 4d exhibited strong selectivity inhibitory activity toward hMAO-B.Figure optionsDownload as PowerPoint slide