Synthesis, characterization and antimicrobial activity of N-acetyl-3-acetyl-5-benzylidene tetramic acid-metal complexes. X-ray analysis and identification of the Cd(II) complex as a potent antifungal agent

Dimitris Matiadis; Dimitrios Tsironis; Valentina Stefanou; Alysha G Elliott; Konstantinos Kordatos; Georgia Zahariou; Nikolaos Ioannidis; Vickie McKee; Angeliki Panagiotopoulou; Olga Igglessi-Markopoulou; John Markopoulos

doi:10.1016/j.jinorgbio.2019.02.008

Synthesis, characterization and antimicrobial activity of N-acetyl-3-acetyl-5-benzylidene tetramic acid-metal complexes. X-ray analysis and identification of the Cd(II) complex as a potent antifungal agent

J Inorg Biochem. 2019 May:194:65-73. doi: 10.1016/j.jinorgbio.2019.02.008. Epub 2019 Feb 21.

Affiliations

¹ National Technical University of Athens, School of Chemical Engineering, Laboratory of Organic Chemistry, Zografou Campus, Athens 15773, Greece. Electronic address: dmatiadis@gmail.com.
² National Technical University of Athens, School of Chemical Engineering, Laboratory of Organic Chemistry, Zografou Campus, Athens 15773, Greece.
³ The Institute for Molecular Bioscience, The University of Queensland, Qld, Australia.
⁴ National Technical University of Athens, School of Chemical Engineering, Laboratory of Inorganic and Analytical Chemistry, Zografou Campus, Athens 15773, Greece.
⁵ Institute of Nanoscience and Nanotechnology, NCSR "Demokritos", Ag. Paraskevi, 15310, Attiki, Greece.
⁶ School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland; Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark.
⁷ Institute of Biosciences and Applications, NCSR "Demokritos", Ag. Paraskevi, 15310, Attiki, Greece.
⁸ Laboratory of Inorganic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimiopolis, 15771 Athens, Greece. Electronic address: jmmarko@chem.uoa.gr.

PMID: 30831391
DOI: 10.1016/j.jinorgbio.2019.02.008

Abstract

This study aims at the further expansion of knowledge on the antimicrobial activities of the tetramic acid moiety and the effect of metal complexation. Complexes of the N-acetyl-3-acetyl-5-benzylidenetetramic acid with Mn, Co, Ni, Cu, Zn and Cd were synthesized and screened against 5 key ESKAPE pathogens (Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa) and 2 fungi (Cryptococcus neoformans and Candida albicans). The cadmium complex was found to effectively inhibit the fungus Cryptococcus neoformans with minimum inhibitory concentration (MIC) of 8 μg/mL, with no human cell toxicity and hemolytic activity within the tested concentration range. The biologically active tetramic acid‑cadmium complex was structurally characterized by single-crystal X-ray analysis. Furthermore, the thermal stability of the ligand and the complexes was investigated along with NMR and EPR studies of the Cd(II) and Co(II) complexes respectively.

Keywords: Antibacterial activity; Antifungal activity; Crystal structure; Metal complex; Pyrrolidine-2,4-dione; Tetramic acid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / toxicity
Antifungal Agents / chemical synthesis
Antifungal Agents / pharmacology*
Antifungal Agents / toxicity
Bacteria / drug effects
Cadmium / chemistry
Coordination Complexes / chemical synthesis
Coordination Complexes / pharmacology*
Coordination Complexes / toxicity
Crystallography, X-Ray
Erythrocytes / drug effects
HEK293 Cells
Hemolysis / drug effects
Humans
Microbial Sensitivity Tests
Mitosporic Fungi / drug effects

Substances

Anti-Bacterial Agents
Antifungal Agents
Coordination Complexes
Cadmium