Synthesis, Structural Characterization and Biological Activity Evaluation of Novel Cu(II) Complexes with 3-(trifluoromethyl)phenylthiourea Derivatives

Int J Mol Sci. 2022 Dec 10;23(24):15694. doi: 10.3390/ijms232415694.

Abstract

Copper complexes with 1,3-disubstituted thiourea derivatives, all containing 3-(trifluoromethyl)phenyl tail and 1-alkyl/halogen-phenyl substituent, were synthesized. The experimental spectroscopic studies and theoretical calculation revealed that two ligands coordinate to Cu(II) in a bidentate fashion via thiocarbonyl S and deprotonated N atoms of thiourea moiety. Such monomers are characteristic of alkylphenylthiourea complexes, whereas the formation of a sandwich-type dimer is observed for halogeno derivatives. For the first time, the structural identifications of CuN2S2-based complexes using experimental and theoretical X-ray absorption near edge structure are demonstrated. The dimeric halogeno derivatives showed higher antimicrobial activity in comparison with alkylphenylthiourea complexes. The Cu(II) complex of 1-(4-chloro-3-nitrophenyl)-3-[3-(trifluoromethyl)phenyl]thiourea was active against 19 strains of methicillin-resistant Staphylococci (MIC = 2 µg/mL). This derivative acted as a dual inhibitor of DNA gyrase and topoisomerase IV isolated from Staphylococcus aureus. Additionally, complexes of halogenphenylthiourea strongly inhibited the growth of mycobacteria isolated from tuberculosis patients, even fourfold stronger than the reference isoniazid. The complexes exerted weak to moderate antitumor activity (towards SW480, SW620, and PC3) being non-toxic towards normal HaCaT cells.

Keywords: ATR-IR; Cu(II) complexes; UV-Vis; XAFS; antimicrobial activity; thiourea.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Coordination Complexes* / chemistry
  • Copper / chemistry
  • DNA Gyrase
  • DNA Topoisomerase IV
  • Humans
  • Phenylthiourea*
  • Thiourea / chemistry
  • Thiourea / pharmacology

Substances

  • Phenylthiourea
  • Anti-Bacterial Agents
  • Thiourea
  • DNA Topoisomerase IV
  • DNA Gyrase
  • Copper
  • Coordination Complexes

Grants and funding

This work was supported in part by PL-Grid (ACK Cyfronet cluster).