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

Abstract

AbstractHeterocyclic 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 Ki 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.