Reactive Oxygen Species Inducing Triazolylpyridine-Based Ru(II)/Ir(III) Complexes for Therapeutically Enhanced Triple-Negative Breast Cancer Treatment
The effectiveness of existing systemic and targeted therapies remains limited in triple-negative breast cancer (TNBC) treatment. Much research has been conducted on reactive oxygen species (ROS)-mediated cancer cell death to overcome the shortcomings of the currently applied chemotherapeutic treatments. Herein, we have developed novel Ru(II)/Ir(III)-mediated triazolylpyridine complexes as ROS inducers. Upon entering the TNBC cells, the Ru(II) complex effectively accumulated in mitochondria and triggered the creation of ROS, facilitating dysfunction of mitochondria and oxidative DNA damage, ultimately causing death of cells through G2/M phase cell cycle arrest. Eventually, this complex induced the upregulation of BAX (pro-apoptotic protein) and downregulation of BCL-2 (antiapoptotic protein) and triggered the caspase 3/9 pathway and released cytochrome <i>c</i> in the cytosol for apoptosis. The complex <b>JRu</b> (Ru<sup>II</sup> triazolylpyridine) significantly reduced the integrity and viability of TNBC 3D spheroids.
Authors
- Samya Banerjee (ORCID: https://orcid.org/0000-0003-4393-4447)
- Priyankar Paira (ORCID: https://orcid.org/0000-0003-1698-4895)
- Suvendu Maity (ORCID: https://orcid.org/0000-0002-9108-1138)
- Annamalai Senthil Kumar
- Prasanta Ghosh (ORCID: https://orcid.org/0000-0002-2925-1802)
- Rajesh Kushwaha (ORCID: https://orcid.org/0000-0002-5724-3623)
- Utpal Das (ORCID: https://orcid.org/0000-0003-2239-7400)
- Debasish Mondal (ORCID: https://orcid.org/0000-0001-8238-7592)
- Bipasha Bose (ORCID: https://orcid.org/0000-0002-2312-9734)
- Binoy Kar (ORCID: https://orcid.org/0000-0002-2059-6900)
- Shanooja Shanavas (ORCID: https://orcid.org/0000-0003-0820-1651)
- Sudheer Shenoy P (ORCID: https://orcid.org/0000-0002-4014-4055)
- Meena Jayaprakash
Institutions
- Yenepoya University (IN)
- Ramakrishna Mission Vidyamandira (IN)
- Technology Centre Prague (CZ)
- Green Technology (US)
- Indian Institute of Technology BHU (IN)
- Vellore Institute of Technology University (IN)
- Banaras Hindu University (IN)
Publication Details
- Journal
- Journal of Medicinal Chemistry
- Published
- 2025-02-05
- DOI
- https://doi.org/10.1021/acs.jmedchem.4c02089
- Citations
- 12
- Primary Topic
- Click Chemistry and Applications
- Type
- article
- Field-Weighted Citation Impact
- 11.23
Funders
- Department of Science and Technology, Ministry of Science and Technology, India
- Ministry of Education, India
- VIT University
- Science and Engineering Research Board