article · Molecules
Researchers have synthesised and characterised two new ruthenium-based complexes containing 2-aminophenyl benzimidazole ligands to evaluate their chemotherapeutic potential. Tests revealed that the compounds interact with DNA through intercalation. Laboratory evaluations on human breast cancer and colorectal cancer cell lines showed that the ruthenium(III) complex displayed the strongest anticancer activity. This compound triggered programmed cell death and halted the cancer cell cycle in the G2/M phase, whilst neither complex damaged healthy liver cells. In animal trials using mice with Ehrlich ascites carcinoma, the ruthenium(III) complex cleared the tumour burden effectively. It induced apoptosis through changes in specific gene and protein markers, reduced oxidative stress, and elevated antioxidant enzyme levels. These effects were achieved with only low levels of liver and kidney toxicity, highlighting the compound as a promising candidate for further anticancer development.
Many existing cancer chemotherapies damage healthy organs alongside tumour cells. This research demonstrates a metal-based compound that targets colorectal and breast cancer cells while leaving healthy liver cells unaffected in laboratory tests. Because it suppressed tumour growth in mice with low toxicity to the kidneys and liver, the compound presents an encouraging foundation for developing safer, more targeted cancer therapies.
This research could support the development of novel metal-based chemotherapeutic drugs for oncology treatments. The prospective end users would be pharmaceutical developers and clinical researchers seeking alternatives to existing toxic platinum-based therapies. Because the compound has only been evaluated in cell cultures and mouse models, it remains at an early preclinical stage of research and requires extensive pharmacokinetic validation and clinical trials before commercial deployment.
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New anticancer ruthenium(II/III) complexes [RuCl<sub>2</sub>(DMSO)<sub>2</sub>(Hapbim)] (<b>1</b>) and [RuCl<sub>3</sub>(DMSO) (Hapbim)] (<b>2</b>) (Hapbim = 2-aminophenyl benzimidazole) have been synthesized and characterized, and their chemotherapeutic potential evaluated. The interaction of the compounds with DNA was studied by both UV-Visible and fluorescence spectroscopies, revealing intercalation of both the Hapbim ligand and the Ru complexes. The in vitro cytotoxicity of the compounds was tested on human breast cancer (MCF7), human colorectal cancer (Caco2), and normal human liver cell lines (THLE-2), with compound (<b>2</b>) the most potent against cancer cells. The cytotoxic effect of (<b>2</b>) is shown to correlate with the ability of the Ru(III) complex to induce apoptosis and to cause cell-cycle arrest in the G2/M phase. Notably, both compounds were inactive in the noncancerous cell line. The anticancer effect of (<b>2</b>) has also been studied in an EAC (Ehrlich Ascites Carcinoma) mouse model. Significantly, the activity of the complex was more pronounced in vivo, with removal of the cancer burden at doses that resulted in only low levels of hepatotoxicity and nephrotoxicity. An apoptosis mechanism was determined by the observation of increased <i>Bax</i> and caspase <i>3</i> and decreased <i>Bcl2</i> expression. Furthermore, (<b>2</b>) decreased oxidative stress and increased the levels of antioxidant enzymes, especially SOD, suggesting the enhancement of normal cell repair. Overall, compound (<b>2</b>) shows great potential as a chemotherapeutic candidate, with promising activity and low levels of side effects.
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DOI: 10.3390/molecules25184284
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