Departamento de Química Inorgánica, Universidade de Santiago de Compostela, Avenida das Ciencias s/n, 15782 Santiago de Compostela, Spain.
Departamento de Ciências da Vida, Faculdade de Ciências e Tecnologia, UCIBIO, Universidade NOVA de Lisboa, 2829-516 Caparica, Portugal.
Inorg Chem. 2021 Mar 15;60(6):3939-3951. doi: 10.1021/acs.inorgchem.0c03763. Epub 2021 Mar 3.
Palladacycles are versatile organometallic compounds that show potential for therapeutic use. Here are described the synthesis and characterization of mono- and dinuclear palladacycles bearing diphosphines. Their biological effect was investigated in A2780, an ovarian-derived cancer line, and in normal dermal fibroblasts. The compounds displayed selective cytotoxicity toward the A2780 cell line. Compound decreased the cell viability through cell cycle retention in G0/G1, triggered apoptosis through the intrinsic pathway, and induced autophagy in A2780 cells. Compound also induced cell cycle retention, apoptosis, and cellular detachment. Notably, compound induced the production of intracellular reactive oxygen species (ROS). Our work demonstrated that compound enters A2780 cells via active transport, which requires energy, while compound enters A2780 cells mostly passively. The potential effect of palladacycles in angiogenesis was investigated for the first time in an in vivo chorioallantoic membrane model, showing that while compound displayed an antiangiogenic effect crucial to fighting cancer progression, compound promoted angiogenesis. These results show that palladacycles may be used in different clinical applications where pro- or antiangiogenic effects may be desirable.
钯环是多功能的有机金属化合物，具有治疗用途的潜力。本文描述了单核和双核钯环的合成和表征，这些钯环带有双膦配体。它们在卵巢来源的癌细胞系 A2780 和正常真皮成纤维细胞中的生物效应进行了研究。这些化合物对 A2780 细胞系表现出选择性细胞毒性。化合物 通过将细胞周期滞留在 G0/G1 来降低细胞活力，通过内在途径触发细胞凋亡，并诱导 A2780 细胞发生自噬。化合物 也诱导细胞周期停滞、细胞凋亡和细胞脱落。值得注意的是，化合物 诱导了细胞内活性氧（ROS）的产生。我们的工作表明，化合物 通过需要能量的主动运输进入 A2780 细胞，而化合物 主要通过被动方式进入 A2780 细胞。首次在体内绒毛尿囊膜模型中研究了钯环在血管生成中的潜在作用，结果表明，虽然化合物 显示出抑制血管生成的作用，这对对抗癌症进展至关重要，但化合物 促进了血管生成。这些结果表明，钯环可用于不同的临床应用，其中可能需要或不需要促血管生成作用。
