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Ruthenium compounds are known to be potential drug candidates since they offer the potential for reduced toxicity. Furthermore, the various oxidation states, different mechanisms of action and ligand substitution kinetics give them advantages over platinum-based complexes, making them suitable for use in biological applications. So, herein, novel ruthenium(II) complexes with metronidazole as ligand were obtained [RuCl(MTNZ)(dppb)(4,4'-Mebipy)]PF

A series of five new ruthenium phosphine/diimine complexes were prepared and characterized by IR, UV–Vis, 1H, 31P{1H} and 13C{1H} NMR spectroscopies, elemental analyses and cyclic voltammetry. Four of the complexes have the general formula ct-[RuCl(L)(dppb)(4,4′-Mebipy)](PF6)n (dppb = 1,4-bis(diphenylphosphino)butane, 4,4′-Mebipy = 4,4′-dimethyl-2,2-bipyridine and L = CO, NO+, NO2− or pyridine), and one has the formula [Ru(NO3)(dppb)(4,4′-Mebipy)]PF6, where NO3− is a bidentate ligand. In addition, the crystal structure of the complex ct-[RuCl(CO)(dppb)(4,4′-Mebipy)]PF6 was elucidated by single-crystal X-ray diffraction analysis, which supported the geometry of the compounds suggested by the 31P NMR experiments. The cytotoxic activity of the synthesized compounds was evaluated against five cancer cell lines: HepG2 (liver), HT144 (melanoma), A549 (lung), MDA-MB-231 (breast) and HCT-9 (colon). Human serum albumin (HSA) and DNA binding experiments were also conducted. The HSA binding constants and thermodynamic parameters suggested spontaneous interactions of the complexes with this protein through van der Waals forces and hydrogen bonding. A spectroscopic titration study indicated that the compounds interacted with ct-DNA, exhibiting binding constants, Kb, on the order of 1.0 × 104 M−1. Additionally, the ruthenium complex containing pyridine displayed cytotoxic activity against HT144, A549, and MDA-MB-231. In addition, it demonstrated pro-apoptotic activity on MDA-MB-231 cells as well as the ability to reduce colony formation. These findings are very promising and have motivated further studies for identifying the molecular target underlying the antitumor activity of the ruthenium(II)/pyridine complex against triple-negative breast cancer.

Herein, four novel ruthenium(II) complexes containing cimetidine as a ligand were obtained, [RuCl(CIM)(dppb)(bipy)]Cl (1), [RuCl(CIM)(dppb)(4,4′-Me-bipy)]Cl (2), [RuCl(CIM)(dppb)(5,5′-Me-bipy)]Cl (3), [RuCl(CIM)(dppb)(phen)]Cl (4), where CIM (cimetidine) = cyano-2-methyl-3-[2-[(5-methyl-1H-imidazol-4-yl) methylsulfanyl] ethyl]guanidine], dppb = 1,4-bis(diphenylphosphine)butane, bipy = 2,2′-bipyridine, 4,4′-Me-bipy = 4,4′-dimethyl-2,2′-bipyridine, 5,5′-Me-bipy = 5,5′-dimethyl-2,2′-bipyridine and phen = 1,10-phenanthroline. The complexes were characterized by elemental analysis; molar conductivity measurements; infrared and UV–Vis spectroscopy; 31P{1H}, 13C and 1H NMR; mass spectrometry and cyclic voltammetry. Density functional theory (DFT) calculations were performed and compared with experimental data. Coordinated cimetidine cleavage was also observed. The cytotoxicity profiles of compounds (1–4) were determined in a glioblastoma cell line (U251-MG), and compared to the free ligand cimetidine, these compounds were able to reduce the viability of U251-MG cells.

Leishmaniasis is a parasitic disease caused by protozoa of the genus Leishmania, which has very limited treatment options and affects poor and underdeveloped populations. The current treatment is plagued by many complications, such as high toxicity, high cost and resistance to parasites; therefore, novel therapeutic agents are urgently needed. Herein, the synthesis, characterization and in vitro leishmanicidal potential of new complexes with the general formula [RuCl3(TMP)(dppb)] (1), [PtCl(TMP)(PPh3)2]PF6 (2) and [Cu(CH3COO)2(TMP)2]·DMF (3) (dppb = 1,4-bis(diphenylphosphino)butane, PPH3 = triphenylphosphine and TMP = trimethoprim) were evaluated. The complexes were characterized by infrared, UV–vis, cyclic voltammetry, molar conductance measurements, elemental analysis and NMR experiments. Also, the geometry of (2) and (3) were determined by single crystal X-ray diffraction. Despite being less potent against promastigote L. amazonensis proliferation than amphotericin B reference drug (IC50 = 0.09 ± 0.02 μM), complex (2) (IC50 = 3.6 ± 1.5 μM) was several times less cytotoxic (CC50 = 17.8 μM, S·I = 4.9) in comparison with amphotericin B (CC50 = 3.3 μM, S·I = 36.6) and gentian violet control (CC50 = 0.8 μM). Additionally, complex (2) inhibited J774 macrophage infection and amastigote number by macrophages (IC50 = 6.6 and SI = 2.7). Outstandingly, complex (2) was shown to be a promising candidate for a new leishmanicidal therapeutic agent, considering its biological power combined with low toxicity.

Herein, novel ruthenium(II) complexes containing 1-methylimidazole as a ligand were obtained with the following formulas: [RuCl(1Meim)(dppb)(bpy)]Cl (1), [RuCl(1Meim)(dppb)(4,4′-DMbpy)]Cl (2), [RuCl(1Meim)(dppb)(5,5′-DMbpy)]Cl (3) and [RuCl(1Meim)(dppb)(phen)]Cl (4) where, 1Meim = 1-methylimidazole, dppb = 1,4-Bis(diphenylphosphino)butane, bpy = 2,2′-bipyridine, 4,4′-DMbpy = 4,4′-dimethyl-2,2′-bipyridine, 5,5′-DMbpy = 5,5′-dimethyl-2,2′-bipyridine and phen = 1,10-phenanthroline. Additionally, crystal structures containing the cations of (1) and (3) were obtained when the counter ion was exchanged, leading to the formation of [RuCl(1Meim)(dppb)(bpy)]PF6 (5) and [RuCl(1Meim)(dppb)(5,5′-DMbpy)]PF6 methanol solvate (6) where PF6 = hexafluorophosphate, showing one 1-methylimidazole molecule coordinated through the imidazole nitrogen, as expected. The complexes were characterized by elemental analysis, molar conductivity, infrared and UV–Vis spectroscopy, 1H, 13C{1H} and 31P{1H} NMR, mass spectrometry and cyclic voltammetry. The interactions of complexes 1–4 with DNA and human serum albumin (HSA) were evaluated, and the cytotoxicity profiles of compounds 1–4 were determined using four different tumor cell lines derived from human cancers (melanoma: HT-144, colon: HCT-8, breast: MDA-MB-231 and lung: A549). A higher cytotoxic activity was observed for compound (3) against non-small cell lung cancer (A549). Complex (3) inhibited the clonogenic capacity and cell cycle progression of A549 cells and induced apoptosis involving mitochondrial pathway activation. Therefore, the data obtained in the present study support further investigations concerning molecular targets of complex (3) in non-small cell lung cancer.