Legna Colina-Vegas

Copper(I)–Phosphine Polypyridyl Complexes: Synthesis, Characterization, DNA/HSA Binding Study, and Antiproliferative Activity

A series of copper(I)-phosphine polypyridyl complexes have been investigated as potential antitumor agents. The complexes [Cu(PPh3)2dpq]NO3 (2), [Cu(PPh3)2dppz]NO3 (3), [Cu(PPh3)2dppa]NO3 (4), and [Cu(PPh3)2dppme]NO3 (5) were synthesized by the reaction of [Cu(PPh3)2NO3] with the respective planar ligand under mild conditions. These copper complexes were fully characterized by elemental analysis, molar conductivity, FAB-MS, and NMR, UV-vis, and IR spectroscopies. Interactions between these copper(I)-phosphine polypyridyl complexes and DNA have been investigated using various spectroscopic techniques and analytical methods, such as UV-vis titrations, thermal denaturation, circular dichroism, viscosity measurements, gel electrophoresis, and competitive fluorescent intercalator displacement assays. The results of our studies suggest that these copper(I) complexes interact with DNA in an intercalative way. Furthermore, their high protein binding affinities toward human serum albumin were determined by fluorescence studies. Additionally, cytotoxicity analyses of all complexes against several tumor cell lines (human breast, MCF-7; human lung, A549; and human prostate, DU-145) and non-tumor cell lines (Chinese hamster lung, V79-4; and human lung, MRC-5) were performed. The results revealed that copper(I)-phosphine polypyridyl complexes are more cytotoxic than the corresponding planar ligand and also showed to be more active than cisplatin. A good correlation was observed between the cytostatic activity and lipophilicity of the copper(I) complexes studied here.

Cytotoxicity and anti-tumor effects of new ruthenium complexes on triple negative breast cancer cells

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype. The high rate of metastasis associated to the fact that these cells frequently display multidrug resistance, make the treatment of metastatic disease difficult. Development of antitumor metal-based drugs was started with the discovery of cisplatin, however, the severe side effects represent a limitation for its clinical use. Ruthenium (Ru) complexes with different ligands have been successfully studied as prospective antitumor drugs. In this work, we demonstrated the activity of a series of biphosphine bipyridine Ru complexes (1) [Ru(SO4)(dppb)(bipy)], (2) [Ru(CO3)(dppb)(bipy)], (3) [Ru(C2O4)(dppb)(bipy)] and (4) [Ru(CH3CO2)(dppb)(bipy)]PF6 [where dppb = 1,4-bis(diphenylphosphino)butane and bipy = 2,2’-bipyridine], on proliferation of TNBC (MDA-MB-231), estrogen-dependent breast tumor cells (MCF-7) and a non-tumor breast cell line (MCF-10A). Complex (4) was most effective among the complexes and was selected to be further investigated on effects on tumor cell adhesion, migration, invasion and in apoptosis. Moreover, DNA and HSA binding properties of this complex were also investigated. Results show that complex (4) was more efficient inhibiting proliferation of MDA-MB-231 cells over non-tumor cells. In addition, complex (4) was able to inhibit MDA-MB231 cells adhesion, migration and invasion and to induce apoptosis and inhibit MMP-9 secretion in TNBC cells. Complex (4) should be further investigated in vivo in order to stablish its potential to improve breast cancer treatment.

Metal–azole fungistatic drug complexes as anti-Sporothrix spp. agents

The new complexes [Cu(PPh3)2(KTZ)2]NO3 (1), [Cu(PPh3)2(CTZ)2]NO3 (2), [Au(KTZ)2]Cl (3), [Au(CTZ)2]Cl (4) and Pt(KTZ)2Cl2 (5) were prepared by reaction of KTZ, CTZ (where CTZ: 1-[(2-chlorophenyl)-diphenylmethyl]-1H-imidazole and KTZ: cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine) and their respective metal salts or metal complexes under mild conditions. They were characterized using NMR, UV-vis and IR spectroscopies, microanalytical analysis and mass spectrometry. Complex (5) was also investigated using computational methods (DFT) to evaluate the geometry configuration around the Pt(II) coordination sphere; the results showed that the trans complex is the most stable one. The antifungal activities of these new compounds 1–5 and some of our reported metal-based azole drug derivatives such as Pt(CTZ)2Cl2 (6), [Au(PPh3)(KTZ)]PF6 (7) and [Au(PPh3)(CTZ)]PF6 (8) were evaluated against sporotrichosis agents (Sporothrix schenckii, Sporothrix brasiliensis and Sporothrix globosa). Their selectivities towards fungal cells were also evaluated. Complexes [Cu(PPh3)2(KTZ)2]NO3 (1), [Cu(PPh3)2(CTZ)2]NO3 (2), [Au(PPh3)(KTZ)]PF6 (7) and [Au(PPh3)(CTZ)]PF6 (8) inhibited fungal growth and killed fungi at concentrations in the nanomolar range and were more active than CTZ or KTZ alone. Microscopy analysis using scanning electron microscopy showed that the complexes 1, 2, 7 and 8 interfered with the cell shape. All the metal–azole complexes tested were more selective for fungi than for mammalian cells and human red blood cells, revealing that they are promising molecules for the development of new antifungal compounds.

Structure/Activity of PtII/N,N-Disubstituted-N'-acylthiourea Complexes: Anti-Tumor and Anti-Mycobacterium tuberculosis Activities

The syntheses, characterization, cytotoxicity against tumor cells and anti-Mycobacterium tuberculosis activity assays of Pt/PPh3/N,N-disubstituted-N’-acylthioureas complexes with general formulae [Pt(PPh3)2(L)]PF6, PPh3 = triphenylphosphine; L = N,N-disubstituted-N’-acylthiourea, are here reported. The complexes were characterized by elemental analysis, molar conductivity, infrared (IR), nuclear magnetic resonance (NMR) (H, C{H} and P{H}) spectroscopy. The P{H} NMR data are consistent with the presence of two PPh3 ligands cis to each other position, and one N,N-disubstituted-N’-acylthiourea coordinated to the metal through O and S, in a chelate form. The structures of the complexes were determined by X-ray crystallography, forming distorted square-planar structures. The complexes were tested in human cell lines carcinomas and also screened with respect to their anti-Mycobacterium tuberculosis activity (H37RvATCC 27294). It was found that complexes with N,N-disubstituted-N’-acylthiourea containing open and small chains as R2 groups show higher cytotoxic and higher anti-Mycobacterium tuberculosis activity than those containing rings in this position.

Synthesis of the [(η6-p-cymene)Ru(dppb)Cl]PF6 complex and catalytic activity in the transfer hydrogenation of ketones

Abstract Catalysis under mild conditions is of great importance to various chemistry areas, particularly for the development of novel active compounds and for natural products modifications, among others. In this study, the synthesis, characterization, and evaluation of the catalytic activity of a new ruthenium(II) compound, [(η6-p-cymene)Ru(dppb)Cl]PF6 (A) where dppb=1,4-bis(diphenylphosphine)butane, is presented. Catalytic activity of the new Ru(II) compound was tested on hydrogen transfer reaction in various substrates, acetophenone, benzophenone, cyclohexanone, and methyl-ethyl-ketone. Potassium hydroxide was used as base, whereas isopropanol served as both solvent and hydrogen source. Samples comprising substrate: base: catalyst at a 200 : 20 : 1 ratio were poured into 5 mm tubes and monitored in situ at 40, 50, and 60 °C in a 600 MHz NMR spectrometer. The complex was active in the transfer hydrogenation of ketones, achieving conversions superior to 90% within 4 h at 60 °C, which suggests under mild conditions. Therefore, in situ monitoring the reactions through 1H NMR was a valuable technique to establish the possible catalytic mechanism of Ru(II) precatalyst.