Cytotoxic effect of ruthenium–arene complexes containing tetrazolo[1,5-a] quinoline derivatives on cervical (HeLa), lung (A549), and colon (HCT116) cancer cell lines

Abstract

On a global scale, cancer ranks as the second most common disease. Lung cancer continues to be a leading cause of cancer-related deaths in men, while cervical cancer remains the fourth most prevalent cancer among women worldwide. In the design of anticancer metallodrugs, new organoruthenium(II) complexes have been synthesized by the complexation of 2-[(R-1,2,3,9b-tetraaza-cyclopenta[a]naphthalen-4-yl methylene)-hydrazonomethyl]-phenol (R-methyl) with [(η⁶-p-cymene)RuCl₂]₂. Molecular structures of ligands AQHS^1–3 and complexes C1–C4 have been confirmed by single crystal X-ray diffraction studies. The ligands behaved as N,N-donors by coordinating through azomethine and tetrazole ring nitrogen atoms to the ruthenium ion. To explore the binding efficacy of the ligands and complexes with Calf-Thymus DNA (CT-DNA) and bovine serum albumin (BSA), absorption and emission titrations were carried out. Among the complexes, C4 exhibited the highest DNA binding affinity via partial intercalation, supported by ethidium bromide displacement and circular dichroism studies. Furthermore, the compounds interacted with BSA by quenching the emission intensity through the static quenching mechanism. Synchronous and three-dimensional fluorescence spectral studies confirmed the interaction of the compounds with the tryptophan amino acid of BSA. Furthermore, the cytotoxicity of complexes C1–C4 was evaluated against cervical (HeLa), lung (A549), and colon (HCT116) cancer cell lines, along with normal lung epithelial cells (L-132). All complexes exhibited potent cytotoxicity against cervical and lung cancer cells, with relatively lower effects on colon cancer cells and minimal toxicity toward normal L-132 cells. Notably, complex C4 demonstrated the most significant anti-proliferative activity in both HeLa and A549 cells with IC₅₀ values of 38.21 µM and 49.42 µM. Fluorescence staining studies confirmed that C4 induces apoptosis, accompanied by characteristic morphological changes. Additionally, C4 disrupted metastatic features, demonstrating a dual role in promoting apoptosis and inhibiting metastasis in cervical and lung cancer cells.