Design and synthesis of novel anti-Alzheimer’s agents: Acridine-chromenone and quinoline-chromenone hybrids

• Seventeen novel acridine-chromenone and quinoline-chromenone hybrids were designed and synthesized.
• All of them were evaluated for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activity.
• Among them, compound (8e) exhibited the most potent inhibitory activity: IC50 = 16.17 μM.
• The most active compound was evaluated for β-secretase and neuroprotective activities.

A novel series of acridine-chromenone and quinoline-chromenone hybrids were designed, synthesized, and evaluated as anti-Alzheimer’s agents. All synthesized compounds were evaluated as cholinesterases (ChEs) inhibitors and among them, 7-(4-(6-chloro-2,3-dihydro-1H-cyclopenta[b]quinolin-9-ylamino)phenoxy)-4-methyl-2H-chromen-2-one (8e) exhibited the most potent anti-acetylcholinesterase (AChE) inhibitory activity (IC50 = 16.17 μM) comparing with rivastigmine (IC50 = 11.07 μM) as the reference drug. Also, compound 8e was assessed for its β-secretase (BACE1) inhibitory and neuroprotective activities which demonstrated satisfactory results. It should be noted that both kinetic study on the inhibition of AChE and molecular modeling revealed that compound 8e interacted simultaneously with both the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE.

Novel acridine-chromenone and quinoline-chromenone hybrids were designed, synthesized, and evaluated for their anti-Alzheimer’s disease activity.Figure optionsDownload as PowerPoint slide