Marques Bárbara, Engrácia Diogo M, Machado João Franco, Coelho Jaime A S, Mendes Filipa, Morais Tânia S
Centro de Química Estrutural, Institute of Molecular Sciences, Faculdade de Ciências, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal.
Centro de Ciências e Tecnologias Nucleares, Instituto Superior Técnico, Universidade de Lisboa, 2695-066 Bobadela LRS, Portugal.
Pharmaceuticals (Basel). 2025 Jan 14;18(1):97. doi: 10.3390/ph18010097.
BACKGROUND/OBJECTIVES: Cancer remains one of the major challenges of our century. Organometallic ruthenium complexes are gaining recognition as a highly promising group of compounds in the development of cancer treatments.
Building on the auspicious results obtained for [Ru(η-CH)(PPh)(bipy)][CFSO] (TM34), our focus has shifted to examining the effects of incorporating bioactive ligands into the TM34 framework, particularly within the cyclopentadienyl ring.
In this study, we report the synthesis and characterization of two new ruthenium(II) complexes with the general formula [Ru(η-CHCCH=R)(PPh)(bipy)][CFSO], where R represents a nicotinic acid derivative (NNHCO(py-3-yl)) (1) or an isoniazid derivative (NNHCO(py-4-yl)) (2). The complexes were fully characterized using a combination of spectroscopic techniques and computational analysis, revealing the presence of -hydrazone isomerism. Stability studies confirmed the robustness of both complexes in biological media, with compound 1 maintaining good stability in buffer solutions mimicking physiological (pH 7.4) and tumor-like (pH 6.8) environments. The cytotoxicity of the complexes was evaluated in vitro in several human cancer cell lines, namely melanoma (A375), alveolar adenocarcinoma (A549), epidermoid carcinoma (A431), and breast cancer (MDA-MB 231).
Both compounds exhibited moderate to high cytotoxic activity, with complex 1 showing a greater propensity to induce cell death, particularly in the A431 and MDA-MB 231 cell lines.
背景/目的：癌症仍然是我们这个世纪的主要挑战之一。有机金属钌配合物作为一类在癌症治疗开发中极具前景的化合物正逐渐获得认可。
基于[Ru(η-CH)(PPh)(bipy)][CFSO]（TM34）所取得的良好结果，我们的重点已转向研究将生物活性配体引入TM34骨架的效果，特别是在环戊二烯基环内。
在本研究中，我们报告了两种通式为[Ru(η-CHCCH=R)(PPh)(bipy)][CFSO]的新型钌（II）配合物的合成与表征，其中R代表烟酸衍生物（NNHCO(py-3-yl)）（1）或异烟肼衍生物（NNHCO(py-4-yl)）（2）。使用光谱技术和计算分析相结合的方法对配合物进行了全面表征，揭示了腙异构现象的存在。稳定性研究证实了两种配合物在生物介质中的稳定性，化合物1在模拟生理（pH 7.4）和肿瘤样（pH 6.8）环境的缓冲溶液中保持良好的稳定性。在几种人类癌细胞系中体外评估了配合物的细胞毒性，即黑色素瘤（A375）、肺泡腺癌（A549）、表皮样癌（A431）和乳腺癌（MDA-MB 231）。
两种化合物均表现出中度至高细胞毒性活性，配合物1显示出更大的诱导细胞死亡倾向，特别是在A431和MDA-MB 231细胞系中。
