In vitro antimycobacterial activity and interaction profiles of diarylthiourea-copper (II) complexes with antitubercular drugs against Mycobacterium tuberculosis isolates

• Published in: Tuberculosis (Edinburgh, Scotland) Vol. 143; p. 102412
• Main Authors: Bielenica, Anna, Głogowska, Agnieszka, Augustynowicz- Kopeć, Ewa, Orzelska-Górka, Jolanta, Kurpios-Piec, Dagmara, Struga, Marta
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.12.2023
• Subjects: Antitubercular Agents - pharmacology; Copper; Drug-resistant; Ethambutol; Humans; Isoniazid - pharmacology; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Non-tuberculous mycobacteria; Synergism; Thiourea copper (II) complexes; Tuberculosis - microbiology; Tuberculosis, Multidrug-Resistant - microbiology; Two-drug combination; Non-tuberculous mycobacteria; Thiourea copper (II) complexes; Two-drug combination; Mycobacterium tuberculosis; Drug-resistant; Synergism
• ISSN: 1472-9792; 1873-281X
• DOI: 10.1016/j.tube.2023.102412

The activity of several halogenated copper (II) complexes of 4-chloro-3-nitrophenylthiourea derivatives has been tested against Mycobacterium tuberculosis strains and strains of non-tuberculous mycobacteria. The compounds were 2–16 times more potent than current TB-drugs against multidrug-resistant M. tuberculosis 210. The 3,4-dichlorophenylthiourea complex (5) was equipotent to ethambutol (EMB) towards M. tuberculosis H37Rv and 192 strains. All derivatives acted 2–8 times stronger than isoniazid (INH) against nontuberculous isolates. In the presence of chosen coordinates, the 2–64 times reduction of MIC values of standard drugs was denoted. The synergistic interaction was found between the complex 4 and rifampicin (RMP), and additivity of 1–5, 8 in pairs with EMB and/or streptomycin (SM) against M. tuberculosis 800 was established. All coordination compounds in combination with at least one drug showed additive activity towards both H37Rv and 192 isolates. In 67% incidences of indifference, the individual MIC of a drug decreased 2-16-fold. One can conclude that the novel thiourea chelates described here are potent hits for further developments of new agents against tuberculosis.