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

• Published in: International journal of molecular sciences Vol. 23; no. 24; p. 15694
• Main Authors: Drzewiecka-Antonik, Aleksandra, Struga, Marta, Głogowska, Agnieszka, Augustynowicz-Kopec, Ewa, Dobrzyńska, Katarzyna, Chrzanowska, Alicja, Wolska, Anna, Rejmak, Paweł, Klepka, Marcin T, Wrzosek, Małgorzata, Bielenica, Anna
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.12.2022; MDPI
• Subjects: Alzheimer's disease; Anti-Bacterial Agents - chemistry; Antiinfectives and antibacterials; Antimicrobial activity; Antimicrobial agents; Antitumor activity; ATR-IR; Biological activity; Comparative analysis; Coordination Complexes - chemistry; Copper; Copper - chemistry; Copper compounds; Cu(II) complexes; DNA Gyrase; DNA topoisomerase; DNA Topoisomerase IV; Drug resistance; Humans; Isoniazid; Ligands; Methicillin; Molecular structure; Oxidation; Phenylthiourea; Prostate cancer; Staphylococcus infections; Structural analysis; Thiourea; Thiourea - chemistry; Thiourea - pharmacology; Thiourea derivatives; Tuberculosis; UV-Vis; X ray absorption; XAFS; Cu(II) complexes; UV-Vis; thiourea; antimicrobial activity; XAFS; ATR-IR
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms232415694

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 CuN S -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 (MIC = 2 µg/mL). This derivative acted as a dual inhibitor of DNA gyrase and topoisomerase IV isolated from . 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.