A facile biodegradable chitosan‐SO3H catalyzed acridine‐1,8‐dione synthesis with molecular docking, molecular dynamics simulation and density functional theory against human topoisomerase II beta and Staphylococcus aureus tyrosyl‐tRNA synthetase

Abstract

An efficient and ecobenign pseudo one-pot multicomponent synthesis of acridine-1,8-diones has been investigated using biodegradable and heterogeneous catalyst, chitosan-SO3H under ambient reaction conditions. The highly proficient reaction of dimedone, aldehydes, and ammonium acetate in aqueous ethanol using chitosan-SO3H catalyst at room temperature showed high yields in short reaction time. The bioactivity of molecules was further studied through molecular docking and molecular dynamics simulations, protein-ligand interaction energy calculations and DFT studies. Among all, compounds 4e, 4f (– 11.8 kcal/mol), 4g, 4x and 4c (– 10.8 kcal/mol), 4d, 4i, 4s were the most potent against Human Topoisomerase II beta (3QX3) and Staphylococcus aureus (S. aureus) tyrosyl-tRNA synthetase (1JIJ), respectively and displayed good binding affinity and interaction pattern. Easy availability of substrate and catalyst, use of biodegradable and recyclable polymeric solid acid catalyst, avoid the use of toxic and metallic reagents, operational simplicity, no need of column chromatography, easy workup, clean reaction profile, high yields (70–95%) and purity in short time period (3–12 min) with wide substrate scope (32 derivatives including 10 novel) and broad spectrum of bioactivity are notable advantages of the present protocol.