Metal Complex Derivatives of Azole: a Study on Their Synthesis, Characterization, and Antibacterial and Antifungal Activities

Keshia F Castillo,Adriana M Celis,Nelson G Nuñez-Dallos,Silvia Restrepo,Homero F Pastrana,Alba G Ávila,John J Hurtado,Nestor J Bello-Vieda

doi:10.5935/0103-5053.20160130

Abstract

Four new zinc complex derivatives of azoles and ligands were synthesized and isolated as white air-stable solids and characterized by elemental analyses, thermogravimetric analysis (TGA), infrared spectroscopy, nuclear magnetic resonance (NMR) and mass spectra. The elemental analysis, theoretical calculations and NMR show that the complexes likely have a 1:1 (M:L) stoichiometry and tetrahedral geometry. To evaluate the biological activity of the complexes and to discuss the role of metal ions and structural properties, the ligands and their metal complexes have been studied. Their antimicrobial activity was determined in vitro by agar-well diffusion and broth microdilution against nine bacterial strains and seven fungal strains with clinical relevance. In vitro assays showed that the complexes exhibited moderate antibacterial and/or antifungal activities. The antimicrobial activity was found to be more active for the metal complexes than the ligands. The metal complexes that contained copper and cobalt, respectively, displayed notable antibacterial and antifungal effects against all the tested bacterial strains. The minimum inhibitory concentration 50 (MIC50) values were in the range 2454-0.7 µg mL-1. Metal complexes were more effective at inhibiting bacteria than fungi. The results could provide a high-potential solution for antimicrobial growth resistance, for both bacteria and fungi.

Highlights

Bacteria such as Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa are the most common pathogens associated with hospital and community-acquired infections, and they are responsible for diseases such as urinary tract infections, pneumonia and bloodstream infections
It is clear that pyrazole, imidazole and indazole derivatives combined with metals have strong antibacterial activity against gram-positive and gram-negative bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), and against fluconazole-resistant fungal species such as C. krusei and A. fumigatus
Ligand bonding to metal ions was confirmed by elemental analyses, FTIR spectroscopy studies, thermogravimetric analysis (TGA) and molecular modeling

Summary

Introduction

Microorganisms, such as bacteria, molds and yeasts that are associated with the surrounding environment, may be related to the development of severe infections in humans.1 Bacteria such as Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa are the most common pathogens associated with hospital and community-acquired infections, and they are responsible for diseases such as urinary tract infections, pneumonia and bloodstream infections.2 Fungal infections are responsible for high rates of mortality and morbidity, primarily in immunosuppressed patients.3 Besides providing resistance against some fungal and bacterial strains, a limited number of compounds are available for the treatment of fungal and bacterial infections.4 In this context, azole derivatives have displayed antifungal and antibacterial activity. Antibacterial and antifungal activities of metal salts, ligands and their metal complexes The losses of HCl in similar complexes were previously reported by Szécsényi et al.44 the decomposition of the other ligand, leaving a residual mass of 11.5%.

Results

Conclusion