In Vitro and In Vivo Anticancer Activities of Water-Soluble Ru(II)(η6- p -cymene) Complexes via Activating Apoptosis Central Regulators and Possibilities of New Antitumor Strategies in Triple Negative Breast Cancers

作者：Shad Man, Haojie Ren, Yimiao Li, Jiaqi Li, Cheng Zou, Abdul Jamil Khan, Jinxia Huang, Yan Xia, Shuang Jia, Jie Wang, Xing Liu, Zhao Guo, Yongmin Zhang, Faiz‐Ur Rahman, Xinyu Li · 发表于：Journal of Medicinal Chemistry · 年份：2025 · DOI：10.1021/acs.jmedchem.4c01699 · 被引用次数：8 · 研究领域：Metal complexes synthesis and properties、Metal-Catalyzed Oxygenation Mechanisms、Ferrocene Chemistry and Applications

In this study, we synthesized 12 monofunctional tridentate ONS-donor salicylaldimine ligand ( L )-based Ru(II) complexes with general formula [(Ru( L )( p -cymene)] + ·Cl – ( C1 - C12 ), characterized by 1 H NMR, 13 C NMR, UV, FT-IR spectroscopy, HR-ESI mass spectrometry, and single-crystal X-ray analysis showing ligand’s orientation around the Ru(II) center. All 12 of these 12 complexes were tested for their anticancer activities in multiple cancer cells. The superior antitumor efficacy of C2, C8, and C11 was demonstrated by reduced mitochondrial membrane potential, impaired proliferative capacity, and disrupted redox homeostasis, along with enhanced apoptosis through caspase-3 activation and downregulation of Bcl-2 expression. In the 4T1 breast cancer orthotopic mouse model, assessment of bioluminescence for metastatic spread, tumor burden, histopathological evaluation, immunohistochemistry (IHC), and hematological profiling and tissue Protein expression of caspase-3, cleaved caspase-3, TNF-α, and bcl-2 demonstrated that C8 treatment led to prolonged survival and suppressed tumor progression in triple negative breast cancer.