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Ru(II)-Fenamic-Based Complexes as Promising Human Ovarian Antitumor Agents: DNA Interaction, Cellular Uptake, and
Tamara Teixeira1,2, Marcos V Palmeira-Mello2, Pedro Henrique Machado1,2
1Department of Chemistry, Institute of Exact and Biological Sciences, Federal University of Ouro Preto (UFOP), 35402-136 Ouro Preto, Minas Gerais, Brazil.
Inorganic Chemistry
|February 18, 2025
Summary
Novel ruthenium(II) complexes with fenamic acid derivatives show potent anticancer activity, effectively targeting cisplatin-resistant ovarian cancer cells and inducing cell death, offering a promising alternative to conventional chemotherapy.
Area of Science:
- Inorganic Chemistry
- Medicinal Chemistry
- Cancer Research
Background:
- Cisplatin resistance in cancer treatment leads to poor patient outcomes.
- Metal-based compounds present a viable strategy to overcome drug resistance.
- Developing novel chemotherapeutic agents is crucial for enhancing treatment efficacy.
Purpose of the Study:
- To synthesize and characterize four novel Ruthenium(II) complexes incorporating fenamic acid derivatives.
- To evaluate the cytotoxicity and antitumor potential of these complexes against various cancer cell lines, including cisplatin-resistant ones.
- To investigate the mechanism of action, cellular uptake, and effects on cell morphology and viability.
Main Methods:
- Synthesis and characterization of four Ru(II) complexes using spectroscopic techniques (FTIR, UV-Vis, NMR, MS) and elemental analysis.
- Cytotoxicity assays (IC50 determination) against ovarian (A2780, A2780cisR), breast (MDA-MB-231), and lung (A549) cancer cell lines.
- Mechanistic studies including DNA interaction analysis, cellular uptake assays, cell morphology observation, colony formation assays, and cell death/organelle damage staining.
Main Results:
- The synthesized complexes [Ru(L)(bipy)(dppp)]PF6, where L is fenamic acid (complex 1), mefenamic acid (complex 2), tolfenamic acid (complex 3), or flufenamic acid (complex 4), were fully characterized.
- Complexes 1-4 demonstrated significant cytotoxicity, particularly against A2780 and cisplatin-resistant A2780cisR ovarian cancer cells.
- Mechanistic studies indicated weak DNA interaction, effective cellular uptake for complexes 1 and 2, induction of cell death, organelle damage, and inhibition of colony formation in A2780 cells.
Conclusions:
- The novel Ru(II)-fenamic acid complexes exhibit promising antitumor activity, especially against cisplatin-resistant ovarian cancer.
- These complexes induce cancer cell death through mechanisms involving organelle damage and altered cellular processes.
- Further investigation of these metal-based compounds could lead to the development of new therapeutic strategies for overcoming drug resistance in cancer.
