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Journal of Inorganic Biochemistry

Journal of Inorganic Biochemistry

IF: 3.79
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Positively-charged, chalcone-hydroxypyrone hybrid ruthenium(II)-arene complexes functionalized with ethacrynic acid: Synthesis, characterizaion, and antitumor effect

Published:22 November 2024 DOI: 10.1016/j.jinorgbio.2024.112778
Yuxin Xuan, Yuxi Yan, Shenghui Li

Abstract

A new family of ethacrynic acid-functionalized, chalcone-hydroxypyrone hybrid ruthenium(II)-arene complexes (4a-4e) have been designed, synthesis and fully characterized by 1H and 13C NMR, ESI-MS, elemental analysis, and melting point tests. The molecular structure of 3a, one of the precursor complexes, has been determined by single-crystal X-ray diffraction. The cytotoxicity of the obtained complexes toward human cancer cell lines such as HeLa, MGC803, A549, MDA-MB-231, and MCF-7 cells have been investigated by MTT assay. Whereas complexes 4d and 4e showed significantly higher cytotoxicity than cisplatin (the positive control group) and complexes 3a-3e. Moreover, complexes 4d and 4e exhibited a certain selectivity (selectivity index: 7.33 and 7.57) toward MCF-7 cells over MCF-10a normal cells. Glutathione S-transferases (GSTs) activity assay indicate that complexes 4d and 4e exhibited higher GST inhibitory activity than ethacrynic acid (EA, the best characterized GST inhibitor), consistent with their higher cytotoxicity. Further mechanistic studies showed that 4e-induced cell apoptosis may be aroused by the production of ROS, the loss of mitochondrial membrane potential and G2/M phase cell arrest in MCF-7 cells. In addition, the in vivo antitumor effect study on the xenograft mouse models of MCF-7 cells reveal that complex 4e significantly inhibited tumor growth with a higher inhibition efficiency of 68.80?%, in comparison with the groups treated with cisplatin (59.25?%). These results highlight the strong possibility to develop positively-charged, chalcone-hydroxypyrone hybrid ruthenium(II)-arene complexes funcionalized with GST inhibitor as promising anticancer agents.

Substances (5)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Trypsin 9002-07-7 C35H47N7O10 454 suppliers $17.70-$24930.00
Thiazolyl Blue 298-93-1 C18H16BrN5S 401 suppliers $7.00-$1596.00
Hoechst 33342 23491-52-3 C27H28N6O 193 suppliers $48.00-$1200.00
2′,7′-Dichlorodihydrofluorescein Diacetate 4091-99-0 C24H16Cl2O7 178 suppliers $33.00-$1947.00
FETUIN 9014-81-7 NULL 66 suppliers $37.07-$4380.00

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