Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 143, Issue -, Pages 1597-1603Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2017.10.058
Keywords
Dasatinib; Cu(II) complex; Cell apoptosis; Telomerase activity
Categories
Funding
- National Natural Science Foundation of China [21261025, 21761033]
- Key Foundation Project of Colleges and Universities in Guangxi [ZD2014108]
- Innovative Team & Outstanding Talent Program of Colleges and Universities in Guangxi [2014-49, 2017-38]
- project of guibei characteristic medicine resources research center of Guangxi Province [KYA201703]
- basic skills improvement project for the young and middle-aged teachers in Guangxi colleges and universities [KY2016YB595]
- State Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China [CMEMR2017-B17]
- [IRT_16R15]
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A new copper(II) complex of dasatinib (DAS) was synthesized and characterized via ESI-MS, UV Vis, IR, single-crystal X-ray diffraction analysis, H-1 and C-13 NMR spectroscopy, and elemental analysis. The composition of the new complex (1) was found to be [Cu(DAS + H)(NO3)(2)(H2O)]NO3 center dot(H2O)center dot(CH3OH). Through MTT assay, it was found that 1 had high cytotoxicity towards A549, HeLa, BEL-7402, Hep-G2, NCI-H460, and MGC80-3 tumor cell lines, with IC50 values in 4.04-13.04 mu M. The Hep-G2 cells were the most sensitive to I. It is worth noting that compared with DAS and cisplatin, 1 not only had higher in vitro anticancer activity but also exhibited greater selective toxicity towards Hep-G2 cells than for normal HL 7702 cells. Experimental results from cell apoptosis analysis, cellular uptake, TRAP-silver staining assay, RT-PCR, western blot, and transfection assays showed that 1 was most likely a telomerase inhibitor that targeted c-myc G-quadruplex DNA. The high cytotoxicity and biological behaviors of 1 could be correlated with the central copper(II) atom in the coordinated mode with DAS. (C) 2017 Elsevier Masson SAS. All rights reserved.
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