Molecular Docking, Synthesis and Antimicrobial Evaluation of 4-[(3 hydroxybenzalidene)amino]antipyrine and its Copper Complex

Abstract

The synthesis and characterization of Schiff base-containing transition metal complexes have gained increasing importance due to their catalytic roles in various reactions and their biological activities. These metal complexes have become crucial in drug design, leading to a growing interest in metal-based drugs. The study aimed to synthesize copper metal complex with a new Schiff base ligand 4-[(3-hydroxybenzalidene)amino]antipyrine derived from 4-aminoantipyrine and 3-hydroxybenzaldehyde, as well as evaluate their antimicrobial activity against gram positive and gram-negative bacterial strains. The ligand and its copper complex were assessed for antimicrobial activity against gram-positive and gram-negative strains utilizing disc diffusion and broth dilution methods. Spectroscopic techniques (UV-Vis, FT-IR, XRD, and EDXRF), solubility tests, and elemental analysis were employed to investigate the ligand and copper complex. The ligand displayed high insolubility in various solvents but had limited solubility in chloroform and methyl chloride. The FTIR spectrum of the Schiff base reveals the presence of aromatic hydrocarbons, imine (C=N), hydroxyl (-OH), secondary amine (C-N), carbonyl (C=O), and vibrations associated with C-O and C-C bonds, reflecting its molecular structure. In the EDXRF analysis, a prominent peak at 7.80 keV corresponding to copper was detected, indicating that copper is the most abundant element found in the ligand. XRD analysis demonstrated distinct crystal structures for both the ligand and its copper complex. The UV-Vis spectra of the ligand exhibited an absorption peak at a UV lambda max of 220 nm, indicating a π→π* transition. In contrast, the absorption peaks observed in the copper complex indicated different transitions compared to the Schiff base. The MIC results indicated the copper complex's stronger antimicrobial activity than the Schiff base against tested bacteria. Molecular docking studies showed that the interaction energies of the synthesized compounds, particularly the ligand and copper complex, surpassed that of the well-known anti-diabetic drug, metformin.