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Less toxic zinc(ii), diorganotin(iv), gallium(iii) and cadmium(ii) complexes derived from 2-benzoylpyridine N , N -dimethylthiosemicarbazone: synthesis, crystal structures, cytotoxicity and investigations of mechanisms of action.
- Source :
-
Toxicology research [Toxicol Res (Camb)] 2018 Jun 28; Vol. 7 (5), pp. 987-993. Date of Electronic Publication: 2018 Jun 28 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- Four metal complexes based on 2-benzoylpyridine N , N -dimethylthiosemicarbazone (Bp44mT) were designed. Free ligand and zinc(ii), diorganotin(iv), gallium(iii) and cadmium(ii) complexes all demonstrated pronounced activity, which was indicated using the growth inhibition test in vitro . Interestingly, most of the compounds were found to be selective against hepatocellular carcinoma (HepG2) cells but had little effect on normal hepatocyte (QSG7701) cells. In particular, Zn(Bp44mT) <subscript>2</subscript> ( 1 ) exhibited toxicity on QSG7701 cells which approximately 12-fold lower than that on HepG2 cells. The studies of mechanisms of action indicated that 1 induced reactive oxygen species (ROS) generation in a dose-dependent manner via the mitochondria transduction pathway. Protein analyses showed that 1 significantly promoted p21 and p53 gene expression, causing caspase-3 activation.
Details
- Language :
- English
- ISSN :
- 2045-452X
- Volume :
- 7
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Toxicology research
- Publication Type :
- Academic Journal
- Accession number :
- 30310676
- Full Text :
- https://doi.org/10.1039/c8tx00127h