Interaction of Pd(II) and Pt(II) Amino Acid Complexes With Dinucleotides

The interaction of the dinucleotides d(ApG) and d(ApA) with [Pd(aa)Cl2], where aa = L- or D-histidine or the methyl ester of L-histidine, and with [Pt(Met)Cl2], where Met = L-methionine was studied by 1H and 13C NMR and CD measurements. In the case of the L-histidine and L-histidineOMe, the reaction with d(ApG) appeared to give the bifunctional adducts Pd(L-Histidine)N1(1)N7(2) and Pd(L-HisOMe)N1(1)N7(2), but the behavior with D-histidine suggested the formation of the monofunctional adduct Pd(D-His)N7(2). The reaction of L-histidine with d(ApA) seemed to form the bimetallic adduct (L-His)PdN7(1)N7(2)Pd(L-His). The Pt(II)-L-methionine complex in both reactions with d(ApG) and d(ApA) seemed to yield mainly adducts Pt(L-Met)N7(1)N7(2) but the existence of adducts Pt(L-Met)N1(1)N7(2) cannot be ruled out

Complexes of Pd(II) and Pt(II) with 9-aminoacridine: reactions with DNA and study of their antiproliferative activity

Four new metal complexes {M = Pd(II) or Pt(II)} containing the ligand 9-aminoacridine (9AA) were prepared. The compounds were characterized by FT-IR and 1H, 13C, and 195Pt NMR spectroscopies. Crystal structure of the palladium complex of formulae [Pd(9AA)(μ-Cl)]2 · 2DMF was determined by X-ray diffraction. Two 9-acridine molecules in the imine form bind symmetrically to the metal ions in a bidentate fashion through the imine nitrogen atom and the C(1) atom of the aminoacridine closing a new five-membered ring. By reaction with phosphine or pyridine, the Cl bridges broke and compounds with general formulae [Pd(9AA)Cl(L)] (where L = PPh3 or py) were formed. A mononuclear complex of platinum of formulae [Pt(9AA)Cl(DMSO)] was also obtained by direct reaction of 9-aminoacridine and the complex [PtCl2(DMSO)2]. The capacity of the compounds to modify the secondary and tertiary structures of DNA was evaluated by means of circular dichroism and electrophoretic mobility. Both palladium and platinum compounds proved active in the modification of both the secondary and tertiary DNA structures. AFM images showed noticeable modifications of the morphology of the plasmid pBR322 DNA by the compounds probably due to the intercalation of the complexes between base pairs of the DNA molecule. Finally, the palladium complex was tested for antiproliferative activity against three different human tumor cell lines. The results suggest that the palladium complex of formula [Pd(9AA)(μ-Cl)]2 has significant antiproliferative activity, although it is less active than cisplatin

La vida que quiero: proyectos de vida aplicando psicología positiva y metodologías visuales

Podeu consultar el document complet a: http://hdl.handle.net/2445/58585Éxito y fracaso escolar conviven diariamente en la escuela. Uno es oportunidad para el otro y viceversa. Combinando la teoría de las fortalezas del carácter, identidad narrativa, teoría de la autodeterminación y otros constructos con metodologías audiovisuales, el programa invita a jóvenes a descubrir sus recursos personales y reescribir su biografía a partir de ellos, de modo de finalmente proyectarlos hacia el futuro en un Proyecto de Vida positivo y realista. Para lograrlo, los alumnos son invitados a auto-observarse, observar a sus compañeros y a entrevistar a sus familiares, aprovechando siempre las representaciones visuales. Esta nueva versión de la propia vida queda plasmada en un relato digital, una secuencia de imágenes que retrata la propia vida pasada, presente y futura, sincronizada con un guion que da cuenta del proceso de convertirse en Persona con Fortalezas del Carácter. Se discuten las dificultades, las oportunidades y los desafíos de su implementación en escuelas en Barcelona, Castelldefels y Viladecans

Studies of the Antiproliferative Activity of Ruthenium (II) Cyclopentadienyl-Derived Complexes with Nitrogen Coordinated Ligands

Four cationic ruthenium(II) complexes with the formula [Ru(η5-C5H5)(PPh3)2]+, with L = 5-phenyl-1H-tetrazole (TzH) 1, imidazole (ImH) 2, benzo[1,2-b;4,3-b′] dithio-phen-2-carbonitrile (Bzt) 3, and [5-(2-thiophen-2-yl)-vinyl]-thiophene-2-carbonitrile] (Tvt) 4 were prepared and characterized in view to evaluate their potentialities as antitumor agents. Studies by Circular Dichroism indicated changes in the secondary structure of ct-DNA. Changes in the tertiary structure of pBR322 plasmid DNA were also observed in gel electrophoresis experiment and the images obtained by atomic force microscopy (AFM) suggest strong interaction with pBR322 plasmid DNA; the observed decreasing of the viscosity with time indicates that the complexes do not intercalate between DNA base pairs. Compounds 1, 2, and 3 showed much higher cytotoxicity than the cisplatin against human leukaemia cancer cells (HL-60 cells)

DNA interaction and cytotoxicity studies of new ruthenium(II) cyclopentadienyl derivative complexescontaining heteroaromatic ligands

Four ruthenium(II) complexes with the formula [Ru(eta(5)-C(5)H(5))(PP)L][CF(3)SO(3)], being (PP = two triphenylphosphine molecules), L = 1-benzylimidazole, 1; (PP = two triphenylphosphine molecules), L = 2,2'bipyridine, 2; (PP = two triphenylphosphine molecules), L = 4-Methylpyridine, 3; (PP = 1,2-bis(diphenylphosphine) ethane), L = 4-Methylpyridine, 4, were prepared, in view to evaluate their potentialities as antitumor agents. The compounds were completely characterized by NMR spectroscopy and their crystal and molecular structures were determined by X-ray diffraction. Electrochemical studies were carried out giving for all the compounds quasi-reversible processes. The images obtained by atomic force microscopy (AFM) suggest interaction with pBR322 plasmid DNA. Measurements of the viscosity of solutions of free DNA and DNA incubated with different concentrations of the compounds confirmed this interaction. The cytotoxicity of compounds 1234 was much higher than that of cisplatin against human leukemia cancer cells (HL-60 cells). IC(50) values for all the compounds are in the range of submicromolar amounts. Apoptotic death percentage was also studied resulting similar than that of cisplatin. (C) 2010 Elsevier Inc. All rights reserved

Synthesis, characterization and antiproliferative activity on mesothelioma cell lines of bis(carboxylato)platinum(IV) complexes based on picoplatin

The synthesis and characterization of a series of picoplatin-based ( picoplatin = [PtCl2(mpy)(NH3)], mpy = 2-methylpyridine), Pt(IV) complexes with axial carboxylato ligands of increasing length are reported. The synthesis is based on the oxidation with hydrogen peroxide of picoplatin to give the cis,cis,trans- [PtCl2(mpy)(NH3)(OH)2] intermediate and then its transformation into the dicarboxylato complexes cis, cis,trans-[PtCl2(mpy)(NH3)(RCOO)2] (R = CH3(CH2)n, n = 0-4) with the corresponding anhydride. Pt(IV) complexes with n = 0-2 were selected to be tested on four malignant pleural mesothelioma (MPM) cell lines, on human mesothelial cells (HMC), and on the cisplatin-sensitive ovarian A2780 cell line along with cisplatin as a metallo-drug reference. In general, the longer the axial chain, the more cytotoxic and selective the Pt(IV) complex is. Pt(IV) analogs show good activity on the MPM cell lines, approaching or in some case bypassing that of cisplatin and represent quite promising drug candidates for the treatment of tumors whose chemoresistance is mainly based on glutathione overexpression, such as MPM

New iron(II) cyclopentadienyl derivative complexes: synthesis and antitumor activity against human leukemia cancer cells

A new family of 'FeII(h5-C5H5)' half sandwich compounds bearing a N-heteroaromatic ligand coordinated to the iron center by a nitrile functional group has been synthesized and fully characterized by NMR and UVeVis spectroscopy. X-ray analysis of single crystal was achieved for complexes 1 and 3, which crystallized in the monoclinic P21/c and monoclinic P21/n space groups, respectively. Studies of interaction of these five new complexes with plasmid pBR322 DNA by atomic force microscopy showed very strong and different types of interaction. Antiproliferative tests were examined on human leukemia cancer cells (HL-60) using the MTT assay, and the IC50 values revealed excellent antiproliferative activity compared to cisplatin

Influence of PPh3 moiety in the anticancer activity of new organometallic ruthenium complexes

The effect of the PPh3 group in the antitumor activity of some new organometallic Ruthenium (II) complexes has been investigated. Several complexes of the type [Ru(II)(Cl)(PPh3)(Lig-N)], [Ru(II)(Cl)2(Lig-N)] (where Lig-N=pyridine derivate) and [Ru(II)(Cl)(PPh3)2], have been synthesized and characterized, and an important increment of the antitumor activity and cytotoxicity of the complexes due to the presence of PPh3 moiety has been demonstrated, affording IC50 values of 5.2 μM in HL-60 tumour cell lines. Atomic Force Microscopy, Circular Dichroism and Electrophoresis experiments have proved that these complexes can bind DNA resulting in a distortion of both secondary and tertiary structures. Ethidium bromide displacement Fluorescence Spectroscopy studies and Viscosity measurements support that the presence of PPh3 group induces intercalation interactions with DNA. Indeed, crystallographic analysis, suggest that intra-molecular π-π interactions could be involved in the intercalation within DNA base pairs. Furthermore, HPLC-MS studies have confirmed a strong interaction between Ruthenium complexes and proteins (Ubiquitin and Potato Carboxypeptidase Inhibitor -PCI-) including slower kinetic due to the presence of PPh3 moiety, which could have an important role in detoxification mechanism and others. Finally, Ion Mobility Mass Spectrometry (IMMS) experiments have proved that there is no change in the structural conformation of the proteins owing to their bonding to Ruthenium complexes. This seems particularly important in the case of PCI, that may be a suitable candidate for vehiculizing these complexes in a selective manner into tumour cells. In agreement with these results, further investigations should be carried out to clarify either there is a favoured binding to DNA or to specific proteins, thus to elucidate their main biological target

A novel orally available inhibitor of focal adhesion signaling increases survival in a xenograft model of diffuse large B-cell lymphoma with central nervous system involvement

Central nervous system dissemination is a relatively uncommon but almost always fatal complication in diffuse large B-cell lymphoma patients. Optimal therapy for central nervous involvement in this malignancy has not been established. In this paper, we aimed to evaluate the therapeutic effect of E7123, a celecoxib derivative that inhibits focal adhesion signaling, in a novel xenograft model of diffuse large B-cell lymphoma with central nervous system involvement. Cells obtained after disaggregation of HT subcutaneous tumors (HT-SC cells) were intravenously injected in NOD/SCID mice. These mice received oral vehicle or 75 mg/kg of E7123 daily until they were euthanized for weight loss or signs of sickness. The antitumor effect of E7123 was validated in an independent experiment using a bioluminescent mouse model. Intravenously injected HT-SC cells showed higher take rate and higher central nervous system tropism (associated with increased expression of beta 1-integrin and p130Cas proteins) than HT cells. The oral administration of E7123 significantly increased survival time in 2 independent experiments using mice injected with unmodified or bioluminescent HT-SC cells. We have developed a new xenograft model of diffuse large B-cell lymphoma with central nervous system involvement that can be used in the pre-clinical evaluation of new drugs for this malignancy. E7123 is a new, well-tolerated and orally available therapeutic agent that merits further investigation since it may improve current management of diffuse large B-cell lymphoma patients with central nervous system involvement

CXCR7 expression in diffuse large B-cell lymphoma identifies a subgroup of CXCR4+ patients with good prognosis

© 2018 Moreno et al.The CXCR4/CXCL12 axis has been extensively associated with different types of cancer correlating with higher aggressiveness and metastasis. In diffuse large B-cell lymphoma (DLBCL), the expression of the chemokine receptor CXCR4 is involved in the dissemination of malignant B cells and is a marker of poor prognosis. CXCR7 is a chemokine receptor that binds to the same ligand as CXCR4 and regulates de CXCR4-CXCL12 axis. These findings together with the report of CXCR7 prognostic value in several tumor types, led us to evaluate the expression of CXCR7 in diffuse large B-cell lymphoma biopsies. Here, we describe that CXCR7 receptor is an independent prognostic factor that associates with good clinical outcome. Moreover, the expression of CXCR7 associates with increased survival in CXCR4+ but not in CXCR4- DLBCL patients. Thus, the combined immunohistochemical evaluation of both CXCR7 and CXCR4 expression in DLBCL biopsies may improve their prognostic value as single markers. Finally, we show that CXCR7 overexpression in vitro is able to diminish DLBCL cell survival and increase their sensitivity to antitumor drugs. Hence, further studies on the CXCR7 receptor may establish its role in DLBCL and the molecular mechanisms that modulate CXCR4 activity.This work was supported by Instituto de Salud Carlos III (co-founding from FEDER) [ FIS PI11/00872, RD12/0036/0071, FIS PI14/00450 to J.S., FIS PI15/00378 to R.M., PIE15/00028 to R.M. and J.S., RD12/0036/0069, PS09/01382 to M.G.D, PI15/01393 to M.A, CD13/00074 to V.P.]; Centro de Investigación Biomédica en Red (CIBER) [CB06/01/1031 and Nanomets3 to R.M. and CB16/12/00233 to M.G.D.]; Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) [2014-SGR-1041, 2014PROD0005 to R.M and 2014-SGR-1281 to J.S]; Fundació La Marató TV3 [416/C/2013-2030 to R.M, 100830/31/32 to J.S and M.G.D.]; Josep Carreras Leukaemia Research Institute [P/AG 2014 to R.M.]; the Health Council of Castilla y León (BIO/SA56/13 and BIO/SA78/15 to M.A.); Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR) [2017FI_B00680 to A.F.]