期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 169, 期 -, 页码 103-110出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2019.02.066
关键词
5 7-dichloro-2-methyl-8-quinolinol; Pm(III) complex; Antitumor activity; Cell apoptosis; Mitochondrial dysfunction
资金
- National Natural Science Foundation of China [21771043, 51572050, 21867017, 21601038, 21261025]
- Guangxi Natural Science Foundation [2018GXNSFBA138021, 2015GXNSFDA139007, 2016GXNSFAA380085]
- Guangxi Key Laboratory of Electrochemical and Magnetochemical Functional Materials [EMFM20162107]
- Key Foundation Project of Colleges and Universities in Guangxi [ZD2014108]
- PhD Research Startup Program of Yulin Normal University [G2017009]
- State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Guangxi Normal University) [CMEMR2018-C8, CMEMR2017-A11]
- Innovative Team & Outstanding Talent Program of Colleges and Universities in Guangxi [2014-49]
Three novel Ln(III) complexes, namely, [Pm(dmbpy)(ClQ)(2)NO3] (1), [Yb(dmbpy)(ClQ)(2)NO3] (2), and [Lu(dmbpy)(ClQ)(2)NO3] (3), with mixed 5,7-dichloro-2-methyl-8-quinolinol (H-ClQ) and 4,4'-dimethyl-2,2'-bipyridyl (dmbpy) chelating ligands were first synthesized. The cytotoxic activity of Ln(III) complexes 1-3, H-ClQ and dmbpy against a panel of human normal and cancer cell lines, namely, human non-small cell lung cancer cells (NCI-H460), human cervical adenocarcinoma cancer cells, human ovarian cancer cells, and human normal hepatocyte cells, were evaluated by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The three novel Ln(III) complexes showed a high in vitro antitumor activity toward the NCI-H460 with IC50 of 1.00 +/- 0.25 nM for 1, 5.13 +/- 0.44 mu M for 2, and 11.87 +/- 0.79 mu M for 3, respectively. In addition, Ln(III) complexes 1 and 2 exerted their in vitro antitumor activity/mechanism mainly via the mitochondrial death pathway and caused a G2/M phase arrest in the following order: 1 > 2. An NCI-H460 tumor xenograft mouse model was used to evaluate the Pm(III) complex 1 in vivo antitumor activity. Pm(III) complex 1 showed a high in vivo antitumor activity, and the tumor growth inhibition rate (IR) was 56.0% (p < 0.05). In summary, our study on Pm(III) complex 1 revealed promising results in in vitro and in vivo antitumor activity assays. (C) 2019 Elsevier Masson SAS. All rights reserved.
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