Design and Synthesis of Nitrogen-Rich Triazole-Based Mononuclear Ru(II) Arene Complexes Toward Anticancer Activities

Abstract

Cancer is a disease marked by uncontrolled cell growth, which can form tumors, invade nearby tissues and spread to other parts of the body (metastasis). Ruthenium complexes are emerging as a promising class of metal-based drugs for cancer treatment, offering an alternative where they exhibit several properties that make them suitable for cancer therapy. Therefore, two mononuclear ruthenium arene complexes [(η⁶-p-cymene)Ru(L)Cl](PF₆) (where L1 = 2,2^/-(4-(1 H-pyrrol-1-yl)-4 H-1,2,4-triazole-3,5-diyl)bis(3-methylpyridine) and L2 = 6,6^/-(4-(1 H-pyrrol-1-yl)-4 H-1,2,4-triazole-3,5-diyl)bis(2-methylpyridine) have been designed and synthesized by substitution reactions from the precursor dimer [Ru(p-cymene)(Cl)(μ-Cl)]₂. Both metal complexes have been successfully characterized through various spectroscopic and analytical tools. The molecular structures of [1](PF₆) and [2](PF₆) were elucidated via single-crystal X-ray diffraction analysis. The redox behaviour of both the ligands and their metal complexes was analysed. In addition, cytotoxicity against cancer cell growth was examined using two human breast cancer cell lines, MDA-MB-231 and MCF-7. Live-cell imaging and sodium 3′-[1-(phenylamino-carbonyl)-3,4-tetrazolium]-bis(4-methoxy-6-nitro) benzene-sulfonic acid hydrate (XTT) assay showed that [1](PF₆) killed MDA-MB-231 and MCF-7 breast cancer cell lines, with IC₅₀ values of 125.9 μM and 117.1 μM, respectively. Comparatively, [1](PF₆) had higher cytotoxicity than [2](PF₆) and can be explored in the design of future tailor-made cytotoxic compounds.