In silico exploration of acetic acid driven multicomponent synthesis: design, characterization, and antioxidant evaluation of spiroacridines and spiroquinolines

Abstract

In this study, a highly efficient green synthetic protocol was developed for the synthesis of spiroacridines and spiroquinolines via a multicomponent reaction of 3,4-methylenedioxyaniline, isatin and cyclic 1,3-diones in glacial acetic acid. This metal-free multicomponent approach offers mild reaction conditions, shorter reaction time and easy product purification without column chromatography. Frontier molecular orbitals (FMOs), various quantum chemical descriptors (QCDs) and molecular electrostatic potential (MEP) surfaces were computed using density functional theory (DFT) with a B3LYP/6-311G+(d,p) basis set. All newly synthesized compounds were screened for their antioxidant properties. The compounds 4a and 4v are the most potent ABTS and DPPH radical scavengers to the standard ascorbic acid. In silico molecular docking studies were conducted to determine the binding affinities of the most potent 4a and 4v with targeted antioxidant protein, LD-carboxypeptidase, which show a strong binding affinity of −10.5 kcal mol⁻¹ and −10.7 kcal mol⁻¹, respectively. The most potent antioxidants 4a and 4v were evaluated for in silico drug-likeness and ADME prediction.