Synthesis, Characterization and Biological Activity of Hydrazones and Their Copper(II) Complexes

With the emergence of multidrug resistant pathogens and hence a lack of potent antibiotics, the search for novel antibacterial agents has become of interest. Hydrazones are known to exhibit biological activity against bacteria, viruses and fungi. Nitrofurantoin is widely used in the treatment of infectious urinary tract diseases as an antimicrobial agent inhibiting metabolic enzymes of several Gram-positive and Gram-negative bacteria. Ftivazide demonstrates potent antimycobacterial activity in the therapy for tuberculosis.

Hydrazones represent a class of synthetically accessible organic compounds possessing versatile coordination chemistry with a wide range of metal ions. Copper is an element of fundamental importance for the formation and functioning of several enzymes, such as cytochrome с oxidase and Cu/Zn superoxide dismutase.

Cu(II) coordination compounds with nitrofurantoin, ftivazide and 4,6-di-tert-butyl-2,3-dihydroxybenzaldehyde derived hydrazones were synthesized and characterized by means of elemental analysis, FT-IR spectroscopy, UV-Vis spectroscopy, NMR spectroscopy and XRD analysis, as well as in vitro biological activity assays. Hydrazones were prepared by the reaction of aromatic hydrazides with 4,6-di-tert-butyl-2,3-dihydroxybenzaldehyde using anhydrous methanol as a solvent.

Formation of Cu(II) complexes with hydrazones might enhance therapeutic efficacy and reduce toxicity of uncomplexed organic ligands. This could be due to the interaction of Cu(II) ion with N,O binding moieties resulting in charge delocalization and overall increase in lipophilicity of the system, which facilitates its cell membrane penetration. Novel copper(II) complexes with antibacterial activity are promising chemotherapeutic agents for medicinal chemistry.