期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 176, 期 -, 页码 175-180出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2017.08.017
关键词
Platinum(IV) complexes; Biotin; Target delivery; Anticancer
资金
- National Natural Science Foundation of China [21601034, 21571033]
- National Science and Technology Major Foundation of China [2015ZX09101032]
- Jiangsu Province Natural Science Foundation [BK20160664]
- Fundamental Research Funds for the Central Universities [2242016k30020]
Three biotinylated platinum(IV) complexes (1-3) were designed and synthesized. The resulting platinum(IV) complexes exhibited effective cytotoxicity against the tested cancer cell lines, especially complex 1, which was 2.0-9.6 -fold more potent than cisplatin. These complexes were found to be rapidly reduced to their activated platinum(II) counterparts by glutathione or ascorbic acid under biologically relevant condition. Additional molecular docking studies revealed that the biotin moieties of all Pt(IV) complexes can effectively bind with the streptavidin through the noncovalent interactions. Besides, introduction of the biotin group can obviously promote the cancer cell uptake of platinum when treated with complex 1, particularly in cisplatin-resistant SGC-7901/Cis cancer cells. Further mechanistic studies on complex 1 indicated that it activated the expression of Bax, and induced cytochrome c release from the mitochondria, and finally activated caspase-3.
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