[RuCl(PPh3)2(tpm)]Cl, 1 的三苯基膦取代反应，以三(吡唑基)甲烷 (tpm) 为配体，与苯丁酸氮芥修饰的吡啶配体 PyCA、3-氨基吡啶 (PyNH2) 和 4-吡啶甲醇 ( PyOH)以高产率提供相应的吡啶配合物2-4。 PyCA是通过4-吡啶甲醇与苯丁酸氮芥酯化初步得到的。新化合物PyCA和2-3通过红外光谱和多核核磁共振光谱进行了表征。另外，通过单晶X射线衍射确定了3的结构。针对一组癌细胞系测定了 2-4 和 PyCA 的体外抗增殖活性，将 2 列为表现最好的化合物。随后使用 2 进行了有针对性的研究，以阐明机制方面，包括评估钌细胞摄取、细胞周期停滞、活性氧 (ROS) 的产生、蛋白质印迹和 DNA 损伤（彗星测试）。总体而言，数据强调 2 提供的抗癌活性主要影响线粒体途径，并可能因 DNA 损伤而产生额外贡献。版权所有 © 2024 作者。由爱思唯尔公司出版。保留所有权利。

Triphenylphosphine substitution reactions of [RuCl(PPh3)2(tpm)]Cl, 1, featuring tris(pyrazolyl)methane (tpm) as ligand, with the chlorambucil-decorated pyridine ligand PyCA, 3-aminopyridine (PyNH2) and 4-pyridinemethanol (PyOH) afforded the corresponding pyridine complexes 2-4 in high yields. PyCA was preliminarily obtained via esterification of 4-pyridinemethanol with chlorambucil. The new compounds PyCA and 2-3 were characterized by IR and multinuclear NMR spectroscopy. Additionally, the structure of 3 was ascertained by single crystal X-ray diffraction. The in vitro anti-proliferative activity of 2-4 and PyCA was determined against a panel of cancer cell lines, outlining 2 as the most performing compound. Targeted studies were subsequently undertaken using 2 to elucidate mechanistic aspects, including the assessment of ruthenium cellular uptake, cell cycle arrest, production of reactive oxygen species (ROS), western blotting and DNA damage (comet test). Overall, data highlight that the anticancer activity provided by 2 primarily affects the mitochondria pathway with a potential additional contribution from DNA damage.Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.