Beatriz S. Parajón-Costa

Risedronate metal complexes potentially active against Chagas disease.

In the search for new metal-based drugs for the treatment of Chagas disease, the most widespread Latin American parasitic disease, novel complexes of the bioactive ligand risedronate (Ris, (1-hydroxy-1-phosphono-2-pyridin-3-yl-ethyl)phosphonate), [M(II)(Ris)(2)]·4H(2)O, where M═Cu, Co, Mn and Ni, and [Ni(II)(Ris)(2)(H(2)O)(2)]·H(2)O were synthesized and characterized by using analytical measurements, thermogravimetric analyses, cyclic voltammetry and infrared and Raman spectroscopies. Crystal structures of [Cu(II)(Ris)(2)]·4H(2)O and [Ni(II)(Ris)(2)(H(2)O)(2)]·H(2)O were solved by single crystal X-ray diffraction methods. The complexes, as well as the free ligand, were evaluated in vitro against epimastigotes and intracellular amastigotes of the parasite Trypanosoma cruzi, causative agent of Chagas disease. Results demonstrated that the coordination of risedronate to different metal ions improved the antiproliferative effect against T. cruzi, exhibiting growth inhibition values against the intracellular amastigotes ranging the low micromolar levels. In addition, this strong activity could be related to high inhibition of farnesyl diphosphate synthase enzyme. On the other hand, protein interaction studies showed that all the complexes strongly interact with albumin thus providing a suitable means of transporting them to tissues in vivo.

Potent in vitro anti-Trypanosoma cruzi activity of pyridine-2-thiol N-oxide metal complexes having an inhibitory effect on parasite-specific fumarate reductase.

In the search for new therapeutic tools against Chagas disease (American trypanosomiasis) palladium and platinum complexes of the bioactive ligand pyridine-2-thiol N-oxide were exhaustively characterized and evaluated in vitro. Both complexes showed high in vitro growth inhibition activity (IC50 values in the nanomolar range) against Trypanosoma cruzi, the causative agent of the disease. They were 39–115 times more active than the antitrypanosomal drug Nifurtimox. The palladium complex showed an approximately threefold enhancement of the activity compared with the parent compound. In addition, owing to their low unspecific cytotoxicity on mammalian cells, the complexes showed a highly selective antiparasite activity. To get an insight into the mechanism of action of these compounds, DNA, redox metabolism (intraparasite free-radical production) and two parasite-specific enzymes absent in the host, namely, trypanothione reductase and NADH-fumarate reductase, were evaluated as potential parasite targets. Additionally, the effect of metal coordination on the free radical scavenger capacity previously reported for the free ligand was studied. All the data strongly suggest that trypanocidal action of the complexes could mainly rely on the inhibition of the parasite-specific enzyme NADH-fumarate reductase.

Spectroscopic, magnetic, and electrochemical behavior of the copper(II) complex of carnosine.

Different physicochemical studies were undertaken with polycrystalline samples of the complex [Cu2(carnosine)2(H2O)2].2H2O. The infrared spectrum was discussed in comparison with that of free carnosine and on the basis of the known structural data. Magnetic susceptibility measurements were performed between 4.2 and 300 K, showing an effective magnetic moment of 1.79 BM. Both the electronic (reflectance) and ESR spectra were compatible with the existence of a dx2-y2 ground state. The axial reversed ESR spectrum could be explained on the basis of a very weak interdimeric coupling mechanism. The electrochemical behavior, investigated by cyclic voltammetry, shows that the complex possesses a very high redox stability. The possible SOD-like activity was tested using the NBT/superoxide reduction assay. The results show a negligible SOD activity.

CRYSTAL STRUCTURE, IR-SPECTRUM AND ELECTROCHEMICAL BEHAVIOUR OF CU(CREATININE)2CL2

Abstract The crystal structure of the little compound has been solved by single-crystal X-ray diffractometry. The CuII ion is located on a two-fold crystallographic axis in a quasi-tetrahedral coordination. The infrared spectrum of the complex was recorded and briefly analyzed in relation to its structural peculiarities. Its electrochemical behaviour was investigated by cyclic voltammetry in methanolic solutions.

Spectroscopic Characterization of an Oxovanadium(IV) Complex of Oxodiacetic Acid and o-Phenanthroline. Bioactivity on Osteoblast-Like Cells in Culture

The oxovanadium(IV) complex of oxodiacetic acid (H2ODA) and o-phenanthroline of stoichiometry [VO(ODA)(ophen)]⋅1.5H2O, which presents the interesting tridentate OOO coordination, was thoroughly characterized by infrared, Raman, and electronic spectroscopies. The biological activity of the complex on the cell proliferation was tested on osteoblast-like cells (MC3T3E1 osteoblastic mouse calvaria-derived cells and UMR106 rat osteosarcoma-derived cells) in culture. The complex caused inhibition of cellular proliferation in both osteoblast cell lines in culture, but the cytotoxicity was stronger in the normal (MC3T3E1) than in the tumoral (UMR106) osteoblasts.

Activity on Trypanosoma cruzi, erythrocytes lysis and biologically relevant physicochemical properties of Pd(II) and Pt(II) complexes of thiosemicarbazones derived from 1-indanones.

American trypanosomiasis or Chagas disease, caused by the protist parasite Trypanosoma cruzi (T. cruzi), is a major health concern in Latin America. In the search for new bioactive compounds, eight Pd(II) and Pt(II) complexes of thiosemicarbazones derived from 1-indanones (HL) were evaluated as potential anti-T. cruzi compounds. Their unspecific cytotoxicity was determined on human erythrocytes. Two physicochemical features, lipophilicity and redox behavior, that could be potentially relevant for the biological activity of these complexes, were determined. Crystal structure of [Pd(HL1)(L1)]Cl·CH(3)OH, where HL1=1-indanone thiosemicarbazone, was solved by X-ray diffraction methods. Five of the eight metal complexes showed activity against T. cruzi with IC(50) values in the low micromolar range and showed significantly higher activity than the corresponding free ligands. Four of them resulted more active against the parasite than the reference antitrypanosomal drug Nifurtimox. Anti-T. cruzi activity and selectivity towards the parasite were both higher for the Pd(II) compounds than for the Pt(II) analogues, showing the effect of the metal center selection on the biological behavior. Among both physicochemical features tested for this series of compounds, lipophilicity and redox behavior, only the former seemed to show correlation with the antiproliferative effects observed. Metal coordination improved bioactivity but lead to an increase of mammalian cytotoxicity. Nevertheless, some of the metal complexes tested in this work still show suitable selectivity indexes and deserve further developments.

Crystal Structure and Spectroscopic Behaviour of Oxoetoxo-bis(5,7-dichloro-8-hydroxyquinolinato)vanadium(V)

Summary. The title compound, a new example of an inorganic ester-like complex, was characterized by spectroscopic and X-ray crystallographic methods. It crystallizes in the triclinic space group P1 (a=9.413(2), b=10.595(3), c=11.783(2) Å, α=103.59(2), β=101.98(2), γ=99.40(2)°, Z=2). The structure was solved employing 2902 independent reflections with I>2σ(I) by direct and Fourier methods and refined by a full-matrix least-squares fit to R1=0.049. Infrared and Raman spectra of the solid compound and the electronic absorption spectra of its acetonitrilic and ethanolic solutions were recorded and are briefly discussed.Zusammenfassung. Die Titelverbindung, ein neues Beispiel eines anorganischen esterähnlichen Komplexes, wurde mit spektroskopischen und Röntgen-Einkristall-Methoden charakterisiert. Sie kristallisiert in der triklinen Raumgruppe P1 (a=9.413(2), b=10.595(3), c=11.783(2) Å, α=103.59(2), β=101.98(2), γ=99.40(2)°, Z=2). Die Struktur wurde aus 2902 unabhängigen Reflexen mit I>2σ(I) durch direkte und Fourier-Methoden gelöst und durch einen least-squares fit zu R1=0.049 verfeinert. Die Infrarot- und Ramanspektren des Festkörpers und die Elektronen-absorptionsspektren seiner Lösungen in Acetonitril und Ethanol wurden aufgenommen und werden kurz besprochen.

Vibrational spectra of bis(maltolato)oxovanadium(IV): a potent insulin mimetic agent.

The FTIR and FT-Raman spectra of the oxovanadium(IV) complex of 3-hydroxy-2-methyl-4-pyrone (maltol) bis(maltolato)oxovanadium(IV) were recorded and briefly discussed by comparison with the spectra of uncoordinated maltol and with some related species.

Spectroscopic and electrochemical behavior of aqua-glycylglycinato-imidazole-copper(II), a model compound for Cu(II)/carnosine interactions

Abstract The title complex appears as a very good model for each of the two subunits which constitute the Cu(II) complex of carnosine, investigated in a previous paper. The electronic (reflectance), vibrational, and ESR spectra of both species were compared in detail. The ESR spectrum shows the typical characteristics of a g-tensor with rhombic symmetry, and the present results confirms that the unusual ESR behavior of the dimeric Cu(II)/carnosine complex were originated in an exchange mechanism. The electrochemical behavior of the complex was investigated by cyclic voltammetry. A comparison of the results with those previously obtained for the Cu(II)/carnosine complex brings new evidence for the existence of a monomeric species in Cu(II)/carnosine solutions at room temperature.

Synthesis and characterization of bistropolonato oxovanadium(IV and V) complexes

Oxovanadium(IV) and oxovanadium(V) complexes of tropolone (Htrp, 2-hydroxy-2,4,6-cycloheptatrien-1-one), of stoichiometry VO(trp)2 and VO(trp)2Cl, were characterized by electronic, infrared, and Raman spectroscopies. Their electrochemical behavior was investigated by cyclic voltamperommetry in dimethylsulfoxide solutions. The magnetic susceptibility of VO(trp)2 was investigated between 2 and 300 K. The vibrational spectra of the related Co(trp)2, Cu(trp)2, and Zn(trp)2 complexes were also analyzed for comparative purposes.