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.
Toxicol Res (Camb)
; 7(5): 987-993, 2018 Sep 01.
Article
in En
| MEDLINE
| ID: mdl-30310676
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)2 (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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Toxicol Res (Camb)
Year:
2018
Document type:
Article
Country of publication: