Design and Anticancer Properties of New Water-Soluble Ruthenium–Cyclopentadienyl Complexes

Abstract

Ruthenium complexes are emerging as one of the most promising classes of complexes for cancer therapy. However, their limited aqueous solubility may be the major limitation to their potential clinical application. In view and to contribute to the progress of this field, eight new water-soluble Ru(II) organometallic complexes of general formula [RuCp(mTPPMS)n(L)] [CF3SO3], where mTPPMS = diphenylphosphane-benzene-3-sulfonate, for n = 2, L is an imidazole-based ligand (imidazole, 1-benzylimidazole, 1-butylimidazole, (1-(3-aminopropyl)imidazole), and (1-(4-methoxyphenyl)imidazole)), and for n = 1, L is a bidentate heteroaromatic ligand (2-benzoylpyridine, (di(2-pyridyl)ketone), and (1,2-(2-pyridyl)benzo-[b]thiophene)) were synthesized and characterized. The new complexes were fully characterized by NMR, FT-IR, UV–vis., ESI-HRMS, and cyclic voltammetry, which confirmed all the proposed molecular structures. The antiproliferative potential of the new Ru(II) complexes was evaluated on MDAMB231 breast adenocarcinoma, A2780 ovarian carcinoma, and HT29 colorectal adenocarcinoma cell lines, showing micromolar (MDAMB231 and HT29) and submicromolar (A2780) IC50 values. The interaction of complex 6 with human serum albumin (HSA) and fatty-acid-free human serum albumin (HSAfaf) was evaluated by fluorescence spectroscopy techniques, and the results revealed that the ruthenium complex strongly quenches the intrinsic fluorescence of albumin in both cases.

Exploiting Co(III)-Cyclopentadienyl Complexes To Develop Anticancer Agents

“…Considering that all complexes 2−4 were able to enter the nuclei (Table 3), the evaluation of the interaction of the complexes with the DNA of the cells (in the case of this study A2780 cells) is really important since most of the chemotherapeutic complexes have as target the DNA. 95 This way, 100 ng of plasmidic DNA (pUC18) were incubated with different concentrations (5,25,50, and 100 μM) of the complexes 2−4 for 24 h. pUC18 incubated with 5 mM Tris−HCl, 50 mM NaCl (pH 7.02), pUC18 incubated with DMSO, and pUC18 incubated with Hind III endonuclease for 2 h were used as controls (Figure S12). The normal conformation of the pDNA is the supercoiled isoform and when both of the chains are cleaved the pDNA adopts a linear isoform.…”

“…Indeed, several examples of ruthenium­(II)-(η 6 -C 6 H 6 ) complexes showed promising in vitro and in vivo antitumor properties against various tumor types, even in cisplatin-resistant cell lines. ,− We have been focusing on developing new half-sandwich cationic complexes derived from the Ru­(II)-(η 5 -C 5 H 5 ) fragment as prospective anticancer agents. These Ru­(II)-(η 5 -C 5 H 5 ) derivatives, containing mono/bidentate heteroaromatic and phosphane ligands, have proven to be strong cytotoxic agents against a large range of cancer cell lines in vitro, ,− revealing in some cases an antimetastatic behavior in vivo. , Nonetheless, and despite these important advances in ruthenium complexes, these compounds still present some toxicity.…”

Recent Trends in the Development of Novel Metal-Based Antineoplastic Drugs

“…Morais and coworkers tested a series of cyclopentadienyl Ru(II) complexes [ 59 ] with monodentate imidazole-based or bidentate heteroaromatic ligands. The investigated substances were very lipophilic.…”

Comprehensive Insights into Medicinal Research on Imidazole-Based Supramolecular Complexes

“…Ruthenium (II) imidazole complexes II42a-e containing water-soluble phosphine showed high to moderate cytotoxicity to A2870, MDAMB231, and HT29 cells, and the A2780 cells were more sensitive to the compounds. All the complexes were highly soluble in water [139]. Groups of naphthalimide can be utilized as DNA intercalators in the anticancer field.…”