Efficient synthesis of chromeno[2,3-b]pyridine derivatives using Zn(OTf)2 as a catalyst: DFT computations, molecular docking and ADME studies

Abstract

An efficient method was developed for the synthesis of chromeno[2,3-b]pyridine derivatives by using Zn(OTf)2 (Zinc trifluoromethanesulfonate) via one-pot [3 + 3] cascade annulation methods using 2-amino-4H-chromen-4-one with a different substituted group (1–6) and trans-chalcone. This strategy offers the pharmacological importance of 2-amino-4H-chromen-4-one derivatives in reaction time and good yields. This approach also brings a different perspective to the literature as an intramolecular cyclization pathway. All computational works were performed at the B3LYP/6–311++G** level of theory. After confirming the optimized structures and comparing the calculated spectroscopic data with corresponding experimental data, the intramolecular interactions were evaluated on the basis of NBO “Natural Bond Orbital” theory. The quantum chemical reactivity features and FMO “Frontier Molecular Orbital” analyses were conducted at the same level of theory. The solvent effect on the reactivity behaviors was also investigated by using the results that were determined by obtaining the different solvent environments. Molecular docking was employed to explore the binding affinities of the compounds against AChE (Acetylcholinesterase), BuChE (Butyrylcholinesterase), and HSA (Human serum albümin). Also, the bioavailability and drug-likeness properties of compounds 1–6 were determined to explore the possible usage in further drug design works. © 2023 Elsevier B.V.