Computational, Hirshfeld surface, and molecular docking analysis of 2-(((4-methoxyphenyl)imino)methyl)-4-nitrophenol: In-vitro anticancer, antimicrobial, anti-inflammatory, and antioxidant studies

Abstract

A Schiff base, 2-(((4-methoxyphenyl) imino) methyl)-4-nitrophenol (1) was synthesized with high yield. We have focused on its computational investigation using density functional theory (DFT) approach with B3LYP/6-311G+(d,p) level and in-vitro pharmacological, antioxidant activity, and molecular docking studies. The computational results were evaluated with experimental FT-IR, UV-Vis, NMR and crystal diffraction data. Moreover, elucidation of molecular electrostatic potential (MEP), natural bond orbital (NBO), global reactivity parameters, frontier molecular orbitals, and density of state of the compound were done. In addition, 3D energy framework, Hirshfeld surface, and ADMET profiles were also performed. The characteristic peak of the azomethine group was found in FT-IR, NMR, powder XRD spectra, and single crystal data. The experimental n → π* and π → π* electronic transitions were well matched with the computed data. The title compound exhibited more binding affinity with the target (1GTV) in molecular docking study. Besides, the studied compound showed similar activity in experimental and docking results as compared to kanamycin. The O⋯H/ H⋯O, H⋯H/ H⋯H, C⋯H/ H⋯C, and N⋯H/ H⋯N contacts were found in the two-dimensional fingerprint plots with 32.1, 33.3, 14.5, and 4.2% contribution. The dispersion energy framework was prevalent over the electrostatic energy framework. Drug like character of 1 was assessed by Lipinski’s rule of five. The studied compound has potential activity against B. megaterium and E. coli bacteria and moderate activity against A. niger fungus. It has promising anti-inflammatory activity and exhibited protective power to stabilize the human red blood cell (HRBC). The title Schiff base offered highest cytotoxic activity with IC50 value of 82.04 μg/mL against A549 lung cancer cells. The title compound showed potential free radical scavenging activity with IC50 value of 6.24 ppm in DPPH scavenging assay.