Catalysis Research and Application Center, İnönü University, 44280 Malatya, Türkiye; Scientific And Technological Research Center, İnönü University, 44280 Malatya, Türkiye.
Biochemistry and Biomaterials Research Laboratory, Department of Chemistry, Faculty of Arts and Science, İnönü University, 44280 Malatya, Türkiye.
J Inorg Biochem. 2024 Dec;261:112719. doi: 10.1016/j.jinorgbio.2024.112719. Epub 2024 Sep 1.
Herein, a series of new Ag(I)-NHC complexes containing 1,3-dioxane group were synthesized by the direct reaction of AgO and benzimidazolium salts in light-free conditions. All Ag(I)-NHC complexes were spectrally characterized using H, C NMR, FT-IR, LC-MS, and elemental analysis. Additionally, the structures of compounds 1a and 1e were elucidated by the single X-ray diffraction techniques. Further, the synthesized Ag(I)-NHC complexes were evaluated for cytotoxicity study on the L-929 cells and the anticancer activity against the HCT 116 and MCF-7 cancer cell lines. Notably, 1a showed significant anticancer activity against HCT 116 with an IC of 6.37 ± 0.92 μg/mL compared to cisplatin (IC = 36.75 ± 1.76 μg/mL). 1c (IC = 3.21 ± 1.96 μg/mL) and 1e (IC = 3.72 ± 1.12 μg/mL) exhibited significant anticancer activity against MCF-7 cells and was similar to cisplatin (IC = 32.17 ± 2.85 μg/mL). Meanwhile, 1a and 1e displayed the highest selectivity index. Most importantly, the cell viability test showed that 1e induced neglectable cytotoxicity (IC = 36.38 ± 2.27 μg/mL) toward L-929 and was similar to cisplatin (IC = 36.11 ± 2.09 μg/mL). The anticancer activities of Ag(I)-NHC complexes vary depending on the substituent group of the silver complex and the cell line type. Moreover, the inhibitory mechanism of 1e was not dependent on caspase-associated apoptosis initiated by the lysosomal-mitochondrial pathway. Taken together, we conclude that this work provides a simple and rapid protocol for the synthesis of Ag(I)-NHC complexes and the featured Ag(I)-NHC complexes have an anticancer drug potential for biomedical applications.
本文在避光条件下，通过 AgO 和苯并咪唑盐的直接反应，合成了一系列含有 1,3-二氧戊环基团的新型 Ag(I)-NHC 配合物。所有 Ag(I)-NHC 配合物均通过 H、C NMR、FT-IR、LC-MS 和元素分析进行光谱表征。此外，通过单晶 X 射线衍射技术阐明了化合物 1a 和 1e 的结构。进一步，对合成的 Ag(I)-NHC 配合物进行了 L-929 细胞的细胞毒性研究和对 HCT 116 和 MCF-7 癌细胞系的抗癌活性评估。值得注意的是，与顺铂（IC = 36.75 ± 1.76 μg/mL）相比，1a 对 HCT 116 表现出显著的抗癌活性，IC 为 6.37 ± 0.92 μg/mL。1c（IC = 3.21 ± 1.96 μg/mL）和 1e（IC = 3.72 ± 1.12 μg/mL）对 MCF-7 细胞表现出显著的抗癌活性，与顺铂（IC = 32.17 ± 2.85 μg/mL）相似。同时，1a 和 1e 表现出最高的选择性指数。最重要的是，细胞活力测试表明，1e 对 L-929 的细胞毒性可忽略不计（IC = 36.38 ± 2.27 μg/mL），与顺铂（IC = 36.11 ± 2.09 μg/mL）相似。Ag(I)-NHC 配合物的抗癌活性取决于银配合物的取代基和细胞系类型。此外，1e 的抑制机制不依赖于溶酶体-线粒体途径引发的 caspase 相关凋亡。综上所述，我们得出结论，这项工作为 Ag(I)-NHC 配合物的合成提供了一种简单快速的方法，具有特色的 Ag(I)-NHC 配合物具有用于生物医学应用的抗癌药物潜力。
