Functionalized Diazabenzo[a]anthracenediones: Regioselective Multicomponent Synthesis and Biological and Computational Studies as Potential Cholinesterase Inhibitors

Abstract

Heterocyclic ketene aminals (HKAs) have been used to synthesize diaza-benzo[a]anthracenedione derivatives through highly efficient one pot three-component cascade reaction from readily available precursors. 2-Hydroxy-1,4-naphthoquinone (HNQ) and aromatic aldehydes are reacted with heterocyclic ketene aminals via Et3N-catalyzed tandem [3+2+1] annulation under solvent-free conditions. These reactions were very smooth, productive with high yield and highly regioselective for the synthesis of novel fused tetracyclic compounds (4 a-4 i). These synthesized compounds were discovered to be potent inhibitors of the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes, with K-i values for BChE ranging from 27.37 +/- 4.70 to 78.06 +/- 6.96 nM and AChE from 59.01 +/- 6.91 to 150.88 +/- 14.84 nM, respectively. Molecular docking studies was carried out to find the interactions of most potent inhibitors.