Central objective in clinical oncology has been the development of therapeutic strategies aimed at effectively triggering apoptosis of different cancer cells. Ruthenium complexes are the leverage and emerged anticancer strategy to combat multiple forms of cancer cells. In this study, we synthesized 12 monofunctional ONS-donor salicylaldimine ligand-based Ru(II)(p-cymene) complexes (C1-C12). These complexes were characterized by 1H NMR, 13C NMR, UV and FT-IR spectroscopy and high-resolution electrospray mass spectrophotometric analysis. The structure of C7 was confirmed in solid state by single crystal X-ray analysis, that revealed the exact orientation of the ligand around Ru(II) center. These complexes were further investigated for their anticancer activity against MDA-MB-231, 4T1, U87MG and HeLa cancer cells. A dose-dependent manner reduction in cell viability and survival rates of cancer cells was observed following treatment with these complexes. We identified that C2, C8, and C11 exhibited the most potent anti-tumor effects among these tested complexes. The results from migration ability and live/dead imaging assays, as well as mitochondrial membrane potential (MMP) and clonogenic potential studies, revealed that these complexes demonstrated higher anti-tumor activities by enhancing caspase-3 and reducing Bcl-2 expression. Using the 4T1 breast cancer orthotopic mouse model, we evaluated the efficacy of the most prominent complex (C8) in 4T1 breast cancer by bioluminescence metastatic windows, tumor weight and volume, hematoxylin and eosin (H&E) staining, immunohistochemistry (IHC) staining and hematological tests. Protein expression revealed apoptosis by up-regulating Caspase-3, cleaved caspase-3, TNF-α and down-regulating Bcl-2. Lasting survival and diminished tumor growth were observed in mice receiving the C8 treatment. These findings demonstrated the potential of those water-soluble monofunctional Ru(II) complexes for triple negative breast cancer treatment.

Dr Shahid Ullah Khan is working as an Assistant Professor Department of Biomedical Sciences, College of Medicine, Dubai Medical University (COM, DMU), Dubai 19099, United Arab Emirates. He earned his Ph.D. degree in 'Genome Wide Association Studies and Post doc from HZAU, Wuhan, and SWU P. R. China in 2019, and 2025, respectively. He is recipient of several fellowships and awards such as: (i) World Top 2 % Scientist (ii) Young Scientist Award 2022, (iii) Asian Rank#01, Health and Biomedical Sciences (Biochemistry) Award ，2024, 2023, and 2022,(iii) World Scientists and University Ranking Award 2021 (iv) Agri Sciences China (Visiting Scientist-2020 at HZAU Wuhan, China, (v) Outstanding Research Awarded-2017 and 2019 ISO HZAU Wuhan China, (vi) OMG-2016 Award by HZAU Wuhan China, and (vii) Best Research Award-2022 by SCI-F (Biochemistry), around the globe. His current research activities are Genome Wide Association Studies, Nanotechnology and Natural Products etc. He has published over 100 research papers in the peer reviewed international journals having 704.6 IF. He has also contributed Seven chapters in the book published by Springer.