Synthesis, Spectral Characterization and Biological Activities of O, O'-Dihydroxyazo Compounds Containing Gallic Acid: Molecular Docking and Dynamics Simulation and MM-PBSA Studies

Abstract

In the investigation, diazonium derivatives of 2-aminophenol, 2-amino-4-methylphenol, 2-amino-4-chlorophenol, and 2-amino-5-nitrophenol reacted with gallic acid to produce four distinct o,o'-dihydroxyazo compounds. Description of the o,o'-dihydroxyazo compounds that were produced identified the substituent spectrum data using UV-Vis, FT-IR, NMR spectroscopy and MS spectrometry methods. The UV-Vis behaviors of compounds in ethanol and DMSO were noted at various pH values. The antioxidant, antimicrobial, and urease inhibitory activities of the compounds were determined spectrophotometrically and compared to standard compounds. The DPPH center dot scavenging and metal chelating activities of compound 4b were 2.17 f 0.04 and 11.62 f 0.64 mu g/mL, respectively. Compounds exhibited an effective antibacterial activity against B. cereus. The urease inhibition capacity of compound 4c (IC50: 4.79 f 0.01 mu g/mL) was more effective than thiourea (IC50: 20.04 f 0.16 mu g/mL). Moreover, molecular docking calculations were used to assess the urease inhibition potentials, inhibition kinetics, and interactions of the synthesized compounds with antimicrobial enzymes and urease. The compounds had substantial impacts on density functional theory (DFT), molecular electrostatic potential (MEP), inhibition kinetics, enzyme inhibition, and PASS prediction tests. For this reason, molecular dynamics simulation and MM-PBSA energy calculation were performed to assess the compounds' stability during urease binding. As a result, the effective pharmacological properties of the newly synthesized o,o'-dihydroxyazo compounds were revealed by different in vitro bioactivity tests and in silico calculations.