Synthesis, characterization, Hirshfeld surface analysis, antioxidant and selective β-glucuronidase inhibitory studies of transition metal complexes of hydrazide based Schiff base ligand

Abstract

The synthesis of N′-[(4-hydroxy-3-methoxyphenyl)methylidene] 2-aminobenzohydrazide (H-AHMB) was performed by condensing O-vanillin with 2-aminobenzohydrazide and was characterized by FTIR, high resolution ESI(+) mass spectral analysis, 1H and 13C-NMR. The compound H-AHMB was crystallized in orthorhombic Pbca space group and studied for single crystal diffraction analysis. Hirshfeld surface analysis was also carried out for identifying short interatomic interactions. The major interactions H…H, O…H and C…H cover the Hirshfeld surface of H-AHMB. The metal complexes [M(AHMB)n] where M = Co(II), Ni(II), Cu(II) and Zn(II) were prepared from metal chlorides and H-AHMB ligand. The bonding was unambigously assigned using FTIR and UV/vis analysis. The synthesized ligand H-AHMB and its metal complexes were studied for β-glucuronidase enzyme inhibition. Surprisingly the metal complexes were found more active than the parent ligand and even the standard drug. Zn-AHMB shown IC50 = 17.3 ± 0.68 µM compared to IC50 = 45.75 ± 2.16 µM shown by d-saccharic acid-1,4-lactone used as standard. The better activity by Zn-AHMB implying zinc based metallodrug for the treatment of diseases associated with β-glucuronidase enzyme. The DPPH radical scavenging activities were also studied for all the synthesized compounds. The Co-AHMB complex with IC50 = 98.2 ± 1.78 µM was the only candidate to scavenge the DPPH free radicals.