Medizinische Chemie

Synthesis, Characterization and Antibacterial Activity of a Tridentate Schiff Base Derived from Cephalexin and 1,6-Hexanediamine and its Transition Metal Complexes

Abstract

Juan Anacona, Yaricruz Pineda, Alina Bravo and Juan Camus

Background: The wide use of the antibiotics resulted in the serious medical problem of drugs resistance and public health concern. Preparation of new synthetic derivatives of antibiotics with novel mechanism of action has become an important task to cope with drug resistanceproblems.

Objectives: The goal of the present study is to prepare a family of new metal(II) coordination compounds of Mn, Co, Ni, Cu and Zn with a Schiff base (HL) derived from the condensation of cephalexin antibiotic with 1,6-hexanediamine and to investigate the antibacterial activity of the free cephalexin and the synthesized complexes against gram positive and gram negative strains.

Methods: Several physicochemical and spectroscopic methods including elemental and thermal analysis, molar conductance and magnetic susceptibility measurements, electronic, FT-IR, EPR and 1H NMR spectral and modelling studies, were used to find out the stoichiometry and binding mode of these complexes. Free cephalexin and cephalexin Schiff base complexes have been screened for antibacterial activity by agar diffusion disc method.

Results: The Schiff base ligand HL behaves as a monoanionic tridentate NNO chelating agent. The mode of bonding and the geometry of the coordination compounds have been confirmed on the basis of spectral and magnetic data which suggested an octahedral geometry for all the complexes. Based on these studies, the general formulae [M(L)(H2O)3][PF6] are proposed for the complexes. The characterization methods revealed that the investigated cephalexin exhibited modification in both solubility and antibacterial activity when they interacted with the metal ions under study. The solubility of cephalexin was remarkably decreased in most of the commonly used solvents on its complexation. The antibacterial activity results indicate that while some of the complexes had more bactericidal activity against some bacteria than the free cephalexin, other complexes exhibited less antibacterial activity.

Conclusions: The antibacterial activity of cephalexin was affected on complexation with metal ions. It was found that the synthesized novel metal complexes are more toxic than the free cephalexin and exhibited promising bactericidal activity against E. coli, S. aureus and K. pneumonia.