研究动态
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基于卡宾和二膦配体的双核金 (I) 络合物:双[2-(二环己基膦基)乙基]胺络合物抑制蛋白酶体活性,降低肺癌细胞中的干细胞标记物和球体活力。

Dinuclear gold(I) complexes based on carbene and diphosphane ligands: bis[2-(dicyclohexylphosphano)ethyl]amine complex inhibits the proteasome activity, decreases stem cell markers and spheroid viability in lung cancer cells.

发表日期:2023 Nov 13
作者: Naike Casagrande, Cinzia Borghese, Giuseppe Corona, Donatella Aldinucci, Muhammad Altaf, Adam A A Sulaiman, Anvarhusein A Isab, Saeed Ahmad, Abdul Malik P Peedikakkal
来源: Stem Cell Research & Therapy

摘要:

三种新的双核金 (I) 配合物 (1-3),含有卡宾 (1,3-双(2,6-二异丙基苯基)咪唑-2-亚基 (IPr)) 和二磷烷配体 [bis(1,2-合成了二苯基膦基)乙烷 (Dppe)、双(1,3-二苯基膦基)丙烷 (Dppp) 和双[2-(二环己基膦基)乙基]胺 (DCyPA)],并通过元素分析和 ESI-MS、中 FT 进行了表征-IR和NMR光谱方法。通过X射线晶体学测定了配合物2和3的结构,结果表明配合物是双核的,具有线性配位的金(I)离子。在肺癌 (A549)、乳腺癌 (MC-F7)、前列腺 (PC-3)、骨肉瘤 (MG-63) 和卵巢癌 (A2780 和 A2780cis) 癌症模型中评估了复合物 (1-3) 的抗癌活性。在所有测试的细胞系中,新复合物的生长抑制作用均高于顺铂。使用二维 (2D) 模型和 3D 多细胞肿瘤球体在 A549 细胞中研究了复合物 3 的作用机制。用复合物3处理A549细胞引起:诱导细胞凋亡和活性氧的产生;细胞周期停滞在G0/G1期;抑制蛋白酶体和 NF-kB 活性;肺癌干细胞标志物(NOTCH1、CD133、ALDH1 和 CD44)的下调。在 A549 肺癌细胞的 3D 模型中,Complex 3 也比顺铂更活跃。© 2023。作者获得生物无机化学学会 (SBIC) 的独家许可。
Three new dinuclear gold(I) complexes (1-3) containing a carbene (1,3-Bis(2,6-di-isopropylphenyl)imidazol-2-ylidene (IPr)) and diphosphane ligands [bis(1,2-diphenylphosphano)ethane (Dppe), bis(1,3-diphenylphosphano)propane (Dppp) and bis[2-(dicyclohexylphosphano)ethyl]amine (DCyPA)], were synthesized and characterized by elemental analysis and, ESI-MS, mid FT-IR and NMR spectroscopic methods. The structures of complexes 2 and 3 were determined by X-ray crystallography, which revealed that the complexes are dinuclear having gold(I) ions linearly coordinated. The anticancer activities of the complexes (1-3) were evaluated in lung (A549), breast (MC-F7), prostate (PC-3), osteosarcoma (MG-63) and ovarian (A2780 and A2780cis) cancer models. Growth inhibition by the new complexes was higher than cisplatin in all cell lines tested. The mechanism of action of complex 3 was investigated in A549 cells using 2-dimensional (2D) models and 3D-multicellular tumor spheroids. Treatment of A549 cells with complex 3 caused: the induction of apoptosis and the generation of reactive oxygen species; the cell cycle arrest in the G0/G1 phase; the inhibition of both the proteasome and the NF-kB activity; the down-regulation of lung cancer stem cell markers (NOTCH1, CD133, ALDH1 and CD44). Complex 3 was more active than cisplatin also in 3D models of A549 lung cancer cells.© 2023. The Author(s), under exclusive licence to Society for Biological Inorganic Chemistry (SBIC).