含金(I/III)配合物的[1,3-二乙基-4,5-二苯基-1H-咪唑-2-亚基]对细胞培养基成分的反应行为及其在癌症根除治疗中的潜在应用意义,Journal of Medicinal Chemistry

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含金(I/III)配合物的[1,3-二乙基-4,5-二苯基-1H-咪唑-2-亚基]对细胞培养基成分的反应行为及其在癌症根除治疗中的潜在应用意义
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2023-06-09 , DOI: 10.1021/acs.jmedchem.3c00589
Paul Kapitza ₁ , Amelie Scherfler ₁ , Stefan Salcher ₂ , Sieghart Sopper ₂ , Monika Cziferszky ₁ , Klaus Wurst ₃ , Ronald Gust ₁

Affiliation

卤代[1,3-二乙基-4,5-二苯基-1 H-咪唑-2-亚基]金(I) (氯 ( 5 ), 溴 ( 6 ), 碘 ( 7 )), 双[1 ,3-二乙基-4,5-二苯基-1 H-咪唑-2-亚基]金(I) ( 8 )和双[1,3-二乙基-4,5-二苯基-1 H-咪唑-2-通过HPLC分析亚基]二卤化金(III)（氯( 9 )、溴( 10 )、碘( 11 ))复合物与细胞培养基成分的关系。还研究了 RPMI 1640 介质中的降解。配合物6与氯化物定量反应生成5，同时7还显示配体乱序为8。无法检测到与不含硫醇的氨基酸的相互作用。然而，谷胱甘肽 (GSH) 立即与5和6反应，生成 (NHC) 金 (I)-GSH 复合物12。最活跃的复合物8在体外条件下稳定并且强烈参与7的生物效应。金 (III) 物种9 – 11被 GSH 完全还原至8并且是前药。所有复合物都经过了对顺铂耐药细胞以及富含癌症干细胞的细胞系的抑制作用测试，并显示出优异的活性。此类化合物对于治疗耐药肿瘤具有极大的意义。

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Reaction Behavior of [1,3-Diethyl-4,5-diphenyl-1H-imidazol-2-ylidene] Containing Gold(I/III) Complexes against Ingredients of the Cell Culture Medium and the Meaning on the Potential Use for Cancer Eradication Therapy

The reactivities of halido[1,3-diethyl-4,5-diphenyl-1H-imidazol-2-ylidene]gold(I) (chlorido (5), bromido (6), iodido (7)), bis[1,3-diethyl-4,5-diphenyl-1H-imidazol-2-ylidene]gold(I) (8), and bis[1,3-diethyl-4,5-diphenyl-1H-imidazol-2-ylidene]dihalidogold(III) (chlorido (9), bromido (10), iodido (11)) complexes against ingredients of the cell culture medium were analyzed by HPLC. The degradation in the RPMI 1640 medium was studied, too. Complex 6 quantitatively reacted with chloride to 5, while 7 showed additionally ligand scrambling to 8. Interactions with non-thiol containing amino acids could not be detected. However, glutathione (GSH) reacted immediately with 5 and 6 yielding the (NHC)gold(I)-GSH complex 12. The most active complex 8 was stable under in vitro conditions and strongly participated on the biological effects of 7. The gold(III) species 9–11 were completely reduced by GSH to 8 and are prodrugs. All complexes were tested for inhibitory effects in Cisplatin-resistant cells, as well as against cancer stem cell-enriched cell lines and showed excellent activity. Such compounds are of utmost interest for the therapy of drug-resistant tumors.

更新日期：2023-06-09

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