Synthesis, structural and antimicrobial studies of type II topoisomerase-targeted copper(II) complexes of 1,3-disubstituted thiourea ligands

Anna Bielenica; Aleksandra Drzewiecka-Antonik; Paweł Rejmak; Joanna Stefańska; Michał Koliński; Sebastian Kmiecik; Bogdan Lesyng; Marta Włodarczyk; Piotr Pietrzyk; Marta Struga

doi:10.1016/j.jinorgbio.2018.01.005

Synthesis, structural and antimicrobial studies of type II topoisomerase-targeted copper(II) complexes of 1,3-disubstituted thiourea ligands

J Inorg Biochem. 2018 May:182:61-70. doi: 10.1016/j.jinorgbio.2018.01.005. Epub 2018 Jan 16.

Affiliations

¹ Chair and Department of Biochemistry, Medical University of Warsaw, 02-097 Warszawa, Poland. Electronic address: abielenica@wum.edu.pl.
² Institute of Physics, Polish Academy of Science, 02-668 Warszawa, Poland.
³ Department of Pharmaceutical Microbiology, Medical University of Warsaw, 02-007 Warszawa, Poland.
⁴ Bioinformatics Laboratory, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warszawa, Poland.
⁵ Biological and Chemical Research Centre, Faculty of Chemistry, University of Warsaw, 02-089 Warszawa, Poland.
⁶ Bioinformatics Laboratory, Mossakowski Medical Research Centre, Polish Academy of Sciences, 02-106 Warszawa, Poland; Department of Biophysics, Faculty of Physics, University of Warsaw, 02-093 Warszawa, Poland.
⁷ Department of Pharmacogenomics, Faculty of Pharmacy, Medical University of Warsaw, 02-097 Warszawa, Poland; Laboratory of Centre for Preclinical Research, Medical University of Warsaw, 02-097 Warszawa, Poland.
⁸ Faculty of Chemistry, Jagiellonian University, 30-387 Kraków, Poland.
⁹ Chair and Department of Biochemistry, Medical University of Warsaw, 02-097 Warszawa, Poland; Laboratory of Centre for Preclinical Research, Medical University of Warsaw, 02-097 Warszawa, Poland.

PMID: 29499458
DOI: 10.1016/j.jinorgbio.2018.01.005

Abstract

A series of Cu(II) complexes of 3-(trifluoromethyl)phenylthiourea derivatives was synthesized. Their structural properties were investigated by spectroscopic techniques (infrared and electron paramagnetic resonance), as well as molecular modeling. All studied coordination compounds are mononuclear complexes containing two chelating ligands bonded to the metal cation via S and deprotonated N atoms. The new chelates were evaluated for their antimicrobial potency. The complex of 1-(3,4-dichlorophenyl)-3-[3-(trifluoromethyl)phenyl]thiourea (3) presented the highest activity against Gram-positive pathogens, even stronger than the activity of its non-complexed counterpart and the reference drug. The compound also prevented the biofilm formation of methicillin-resistant and standard strains of staphylococcal cocci. The title derivatives were found to be effective inhibitors of DNA gyrase and topoisomerase IV isolated from Staphylococcus aureus. The binding modes of the ligand L3 with DNA gyrase and topoisomerase IV were presented.

Keywords: Copper complexes; DNA gyrase; Docking; FTIR; Thiourea.

Publication types

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

MeSH terms

Anti-Infective Agents / chemistry*
Anti-Infective Agents / pharmacology*
Biofilms / drug effects
Copper / chemistry*
DNA Gyrase / metabolism
DNA Topoisomerase IV / metabolism
DNA Topoisomerases, Type II / metabolism*
Enzyme Activation / drug effects
Thiourea / chemistry*

Substances

Anti-Infective Agents
Copper
DNA Topoisomerase IV
DNA Gyrase
DNA Topoisomerases, Type II
Thiourea