Toxicology and bioactivities of CO-releasing molecules based on cobalt complexes
10.16438/j.0513-4870.2015-0849
- VernacularTitle:基于羰基钴一氧化碳释放分子的毒性及生物活性研究
- Author:
Ya-guo GONG
1
;
Tao-feng ZHANG
1
;
Meng LI
1
;
Quan-yi ZHAO
1
;
Dian HE
1
;
Na XI
1
;
Jie CHENG
2
;
Yong-lin CHEN
3
;
Bin LIU
4
Author Information
1. Institute of Medicinal Chemistry, School of Pharmacy, Lanzhou 730000, China
2. GLP Lab Centre, School of Basic Medicine, Lanzhou 730000, China
3. The First Hospital, Lanzhou 730000, China
4. School of Stomatology of Lanzhou University, Lanzhou 730000, China
- Publication Type:ORIGINAL ARTICLES
- Keywords:
cobalt;
CO-releasing molecule;
antitumor;
anti-inflammatory
- From:
Acta Pharmaceutica Sinica
2016;51(3):425-
- CountryChina
- Language:Chinese
-
Abstract:
Complexes containing cobalt and carbon monoxide ligands, CO releasing molecules (CORMs), have the potential of anti-tumor and anti-inflammatory. In this paper, three hybrid CORMs 1-3 were synthesized and tested for their toxicology in vivo and bioactivities. The results suggest that the complexes have a long half-life in the range of 43-53 min; their oral LD50 to mouse are between 1 500 mg·kg-1 and 5 000 mg·kg-1. After the successive administration, complex 1 exhibited a toxic activity in rats' liver, and induced an injury to liver cells. Complex 1 had a strong growth inhibition activity (IC50 36.20 μmol·L-1 and 39.25 μmol·L-1) in both HeLa cells and HepG2 cells, complex 2 displayed a lower activity in the inhibition of HeLa cells proliferation than the control 5-FU (IC50 114.19 μmol·L-1), but had a higher activity in the inhibition of HepG2 cells than the control 5-FU (IC50 171.34 μmol·L-1). The anti-inflammatory study suggests that all of them reduce intracellular nitrite level, complexes 1 and 2 have a stronger activity than complex 3. Their anti-inflammatory activity attributes to the CO molecules of the CORMs, which was confirmed by comparison with the corresponding ligand.
