Synthesis, Characterization and Biological Studies of 3d-Metal Complexes of Schiff Bases of Aminoglycosides and ß-Lactam Antibiotics

Abstract

The menace of drug resistance has been haunting the human world in the recent years and there is an urgent need to discover new chemotherapeutic agents with novel bioactivities and functionalities to address the severe challenges of multi drug resistance. Over a few decades of intensive research on metal-based drugs, Schiff base metal complexes have been considered as the active field of research in the coordination chemistry. The present research work evaluates the bio-functional activities of some aminoglycosides and β-lactam antibiotics in their derived form. Their structural modification by the formation of Schiff base and metal complexes, and their correlation with bio-functional activities has been a subject of much interest in the medicinal chemistry research. In view of this, three novel Schiff base ligands (KMAXC, AXCPC3, and AXCPC2) have been prepared and complexed with four transition metal ions viz. Co +2 , Ni +2 vii

, Cu +2 and Zn +2 . The ligands and complexes were fully characterized with various physicochemical and spectroscopic techniques, like CHNS analysis, conductivity measurement, melting point measurement, FT-IR, H NMR, 13 C NMR, electronic absorption, mass spectrometry, magnetic susceptibility and EPR studies.

Thermal stability and kinetic properties of the complexes were analyzed by thermogravimetric and differential thermal analysis (TGA/DTA) technique. The Coats-Redfern method was applied to extract thermodynamic parameters to explain the kinetic behavior of the complexes. Thermal data revealed high thermal stability and non-spontaneous nature of the various decomposition steps in most of the complexes.

The crystalline nature of the complexes was checked by powder X-ray diffraction study. XRPD data were analyzed in X'pert high score software and the diffractograms were carefully analyzed to extract the information about the nature of complexes. Some complexes were found crystalline and some were amorphous. The cell parameters and space group of the complexes were investigated by computing data in CHECKCELL and CRYSFIRE program package software. The surface morphology of the ligands and complexes were evaluated by scanning electron microscopy (SEM) 1

study and revealed their varying surface structures. The evaluated geometry of the complexes by spectroscopic techniques has been further supported by the information gathered from the molecular modeling study. The structure optimization by MM force field calculation was achieved by running the proposed molecular structures in Cs Chem 3D Ultra-11 and Argus Lab 4.0.1 software program.

The biological potency of the synthesized compounds was investigated by antibacterial activity study, which was done by modified Kirby-Bauer paper disc diffusion technique. For this purpose, clinical strains of both gram-positive and gram negative bacteria have been

isolated and cultured in the laboratory. They have been interacted with synthesized compounds at variable concentrations in a solution prepared in DMSO. In most of the study, metal complexes of the prepared Schiff base ligands were found biologically active with enhanced potency, compared to the free ligand and starting compounds.