RESUMO
9-cis-Retinal thiosemicarbazone and its Co(III), Ni(II) and Cu(II) complexes are synthesized and characterized. Central Co(III) atom is in an octahedral environment while Ni(II) and Cu(II) atoms are in a square planar environment. DNA binding constants and spectroscopic data show an intercalative behavior for the nickel complex; an external binding mode is envisaged for the ligand and its copper complex. No DNA interaction can be hypothesized for the cobalt complex. The free ligand and its Ni(II) and Cu(II) complexes have a good lipophilic degree for an efficient uptake by the cells. The metal complexes exhibit a proliferation inhibition action against cell line U937 at micromolar concentration. Cu(II) complex also induces apoptosis, while Ni(II) complex has a strong interaction with CT-DNA.
Assuntos
Proliferação de Células , DNA/química , Metais/química , Retinoides/química , Apoptose , Modelos Moleculares , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
By reacting thiosemicarbazides substituted on the aminic nitrogen with both alkyl or aryl groups, and methyl pyruvate a new group of methylpyruvate thiosemicarbazones (Hmpt) derivatives was obtained. These ligands were then treated with copper and zinc inorganic salts. All isolated compounds were characterized using spectroscopic methods. The single crystal structural analysis of the ligands Me-Hmpt x 0.5H2O 1, Et-Hmpt x H2O 2, Ph-Hmpt 5, Meph-Hmpt 6 showed that only compound 6 presents significant deviation from planarity. The X-ray structure of [Zn(Me-Hmpt)Cl2] x H2O 8 showed that in this complex Me-Hmpt behaves as a neutral ligand SNO terdentate and that the penta coordination is achieved by chloride ions according to spectroscopic and elemental analyses. On the basis of the analytical data the same behavior is proposed for the other zinc complexes. All the ligands in copper complexes seem to be monodeprotonated; nevertheless the same SNO behavior is expected. Tests on cell proliferation of human leukemic cell line U937 showed that the copper complex Cu(Et-mpt)Cl x H2O is the most active compound among those reported even though it is not able to induce apoptosis.
Assuntos
Cobre/química , Tiossemicarbazonas/química , Zinco/química , Apoptose , Divisão Celular/efeitos dos fármacos , Cristalografia , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Espectrofotometria Infravermelho , Tiossemicarbazonas/síntese química , Tiossemicarbazonas/farmacologia , Células Tumorais CultivadasRESUMO
The synthesis, spectroscopic studies, x-ray crystal structure, and biological properties of the complex [Cu(H2L)(OH2)Cl]Cl (1) (H2L = pyridoxal thiosemicarbazone) are reported. The compound crystallizes in space group P2(1)/n, a = 12.128(2), b = 9.096(2), c = 13.592(2) A, beta = 108.65(2) degrees, U = 1420.7 A3, and Z = 4. The molecular structure consists of discrete cations [Cu(H2L)(OH2)Cl]+ and Cl- anions. Each copper atom is in an approximately square pyramidal environment involving the phenolic oxygen, the imine nitrogen, the sulphur, and a water oxygen in the equatorial positions, while a chlorine atom occupies the axial position. The structure of this complex is compared to that of the dimeric [(Cu(HL)(OH2))2]Cl2.2H2O (2) obtained under different experimental conditions, to that of a Co(III) complex with the same ligand [Co(HL)L].4.5H2O (3) and to that of the free ligand H2L, especially in relation to its biological activity. Compounds 1 and 2 have not antiviral action in vitro with respect to RNA viruses, show an inductive effect on Friend erythroleukemia cells (FLC), erythroid differentiation and a suppressive effect regarding FLC proliferation. Complex 3 and the free ligand do not have biological activity.
Assuntos
Compostos Organometálicos/química , Tiossemicarbazonas/química , Animais , Diferenciação Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Cristalização , Cristalografia por Raios X , DNA/biossíntese , Vírus da Leucemia Murina de Friend , Leucemia Eritroblástica Aguda/patologia , Substâncias Macromoleculares , Camundongos , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/farmacologia , Vírus de RNA/efeitos dos fármacos , Espectrofotometria Infravermelho , Tiossemicarbazonas/síntese química , Tiossemicarbazonas/farmacologia , Replicação Viral/efeitos dos fármacosRESUMO
Three new complexes of transition metals as copper, nickel and cobalt with 5-formyluracil thiosemicarbazone (H3ut) have been synthesised and characterised by single-crystal X-ray diffraction. In all compounds the ligand behaves as SNO terdentate. In the copper complex the coordination geometry is square pyramidal with the ligand lying on the basal plane and two water molecules that complete the metal environment, the nickel compound is surrounded by six donor atoms (three of the ligand, two water oxygen atoms and a chlorine atom) in an octahedral fashion, and cobalt also shows an octahedral geometry but determined only by two terdentate ligand molecules. These three compounds have been tested on human leukemic cell lines K562 and CEM. The nickel and cobalt complexes have demonstrated low activity in cell growth, while the copper complex that is more active has been tested also on a third leukemic human cell line (U937), but it was not able to induce apoptosis on all cell lines.
Assuntos
Divisão Celular/efeitos dos fármacos , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia , Uracila/análogos & derivados , Uracila/química , Uracila/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Cobalto/química , Cobalto/farmacologia , Cobre/química , Cobre/farmacologia , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Estrutura Molecular , Mutagênicos/síntese química , Mutagênicos/química , Mutagênicos/farmacologia , Níquel/química , Níquel/farmacologia , Tiossemicarbazonas/síntese química , Células Tumorais Cultivadas , Uracila/síntese químicaRESUMO
New thiosemicarbazones (1-7), derived from p-fluorobenzaldehyde and differently substituted thiosemicarbazides, were synthetized and characterized by means of NMR and IR techniques. The p-fluorobenzaldehyde thiosemicarbazone Hfbt (1), the p-fluorobenzaldehyde 4-phenylthiosemicarbazone Ph-Hfbt (4) and complex [Ni(fbt)2] (8) were also characterized by X-ray diffractometry. Molecules 1 and 4 consist of two units: the p-fluorobenzaldehyde residue and the thiosemicarbazonic chain. In the reaction of 1 with NiAc2.4H2O, complex 8 was afforded. The molecular structure of 8 consists of the neutral molecules [Ni(fbt)2] with the metal placed on a symmetry centre. The coordination results in a square planar configuration and involves the sulphur atom and the hydrazine nitrogen atom of the two ligands in a trans configuration. Moreover, for compounds 1, 2, 4, and 8, assays of proliferation inhibition and apoptosis tests in vitro on human leukemia cell line U937 were carried out.
Assuntos
Apoptose/efeitos dos fármacos , Benzaldeídos/síntese química , Níquel , Tiossemicarbazonas/síntese química , Benzaldeídos/química , Benzaldeídos/farmacologia , Divisão Celular/efeitos dos fármacos , Cristalografia por Raios X , Humanos , Indicadores e Reagentes , Modelos Moleculares , Conformação Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Compostos Organometálicos/farmacologia , Relação Estrutura-Atividade , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia , Células U937 , Difração de Raios XRESUMO
The reaction of zinc chloride, acetate, or perchlorate with two bis(thiosemicarbazones) of 2,6-diacetylpyridine [H2daptsc = 2,6-diacetylpyridine bis(thiosemicarbazone) and H2dapipt = 2,6-diacetylpyridine bis(hydrazinopyruvoylthiosemicarbazone)] leads to the formation of four novel complexes that have been characterized by spectroscopic studies (NMR, IR) and biological properties. The crystal structures of the two compounds--[Zn(daptsc)]2.2DMF (1) and [Zn(H2dapipt)(OH2)2](CIO4)2.3H2O (2)--also have been determined by x-ray methods from diffractometer data. Compound (1) is dimeric and the two zinc atoms have a distorted octahedral coordination. The ligand is deprotonated. In compound (2), the coordination geometry about zinc is pentagonal--bipyramidal and the ligand is in the neutral form. The molecular structure of (2) consists of cations [Zn(H2dapipt)(OH2)]2+, CIO4- disordered anions, and three water molecules of solvation. Biological studies have shown that the ligands and the complexes Zn(daptsc).1/2EtOH and Zn(H2daptsc)Cl2 have an effect in vitro on cell proliferation and differentiation (inhibition); both are concentration dependent. [Zn(daptsc)]2.2DMF (1) shows the effects at lower concentration values with respect to other compounds.
Assuntos
Tiossemicarbazonas/química , Compostos de Zinco/química , Divisão Celular/efeitos dos fármacos , Cristalografia por Raios X , Eritrócitos/efeitos dos fármacos , Eritropoese/efeitos dos fármacos , Vírus da Leucemia Murina de Friend , Espectroscopia de Ressonância Magnética , Piridinas/química , Piridinas/farmacologia , Espectrofotometria Infravermelho , Tiossemicarbazonas/farmacologia , Células Tumorais Cultivadas , Compostos de Zinco/farmacologiaRESUMO
Three Cu(II) co-ordination compounds with a novel ligand, 5-formyluracil thiosemicarbazone (H3ut), have been synthesised and characterised by single-crystal X-ray diffraction and subsequently tested in vitro on human leukemic cells. The crystal structures revealed, in all three cases, a square pyramidal co-ordination geometry of the copper atom with the ligand lying on the basal plane and behaving as an SNO terdentate ligand. These three compounds have been tested on human leukemic cell line K562 and CEM. In these experiments the complexes have demonstrated to inhibit cell growth and one of them to induce apoptosis. In the paper we also report the spectrophotometric characterization of the free ligand.
Assuntos
Cobre , Compostos Organometálicos/síntese química , Uracila/análogos & derivados , Apoptose/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X , Humanos , Leucemia , Modelos Moleculares , Compostos Organometálicos/química , Compostos Organometálicos/toxicidade , Tiossemicarbazonas/síntese química , Tiossemicarbazonas/química , Tiossemicarbazonas/toxicidade , Células Tumorais Cultivadas , Uracila/síntese química , Uracila/química , Uracila/toxicidadeRESUMO
Especially in the old patients (over 70 years) the incisional hernias represents an invalidating pathology whose treatment, for the high incidence of associated diseases of respiratory and cardiocirculatory apparatus in the aged, offers difficulties connected both to surgical methods and to the perioperative evaluation and preparation of patients. The infections of the surgical incision are very important in the pathogenesis of these diseases. In order to reduce the incidence of incisional hernias the systematic use of perioperative antibiotic therapy is desirable in every operation of abdominal surgery. In order to offer the best guarantees of recovery and to improve the postoperative course of patients, the perioperative antibiotic prophylaxis, together with the use of synthetic prosthesis material, is also essential at the moment of surgical correction of incisional hernia. Although the incisional hernia may sometimes stay silent and asymptomatic for years, it inevitably ends sup by representing a reason for acute and subacute pathologic events; an early surgical treatment is therefore desirable once the incisional hernia has been diagnosed. By this way it is possible to avoid the treatment in the old patients, as the old age is a less favourable period for people who have to be subjected to a surgical operation.
Assuntos
Hérnia Ventral , Fatores Etários , Idoso , Feminino , Hérnia Ventral/etiologia , Hérnia Ventral/cirurgia , Humanos , Masculino , Complicações Pós-Operatórias , Infecção da Ferida Cirúrgica/complicaçõesRESUMO
Thiosemicarbazones are a wide group of organic derivatives whose biological activities are a function of the parent aldehyde or ketone and of the coordination metal type. Some thiosemicarbazones possess a broad spectrum of potentially useful chemotherapeutic properties (antitumor, antibacterial, antiviral, antimalarial). The present study reports the biological effects of pyridoxal thiosemicarbazone, H2L, and relative complexes with copper, [(Cu(HL)(OH2))2]++ and with cobalt, [Co(III)(L)(HL)] on the differentiation of Friend erythroleukemia cells (FLC). They are murine proerythroblasts chronically infected by a producing Friend leukemia virus complex; their exposure to dimethylsulfoxide (Me2SO) or other chemical agents induces these cells to terminal erythroid differentiation, therefore these cells represent a good model of differentiation in vitro. Here we describe induction differentiation experiment of pyridoxal thiosemicarbazone and relative complexes of copper and cobalt on FLC performed with concentrations of 50 ug/ml (ligand), 2 ug/ml (complexes). These have little effects on cell proliferation at doses used in these experiments. Higher doses have evident cytotoxic effects. The treatment with the copper complex induces a moderate differentiation of FLC and enhances effects on erythroid differentiation of Me2SO-induced FLC. On the contrary H2L and [Co(III)(L)(HL)] haven't inducing effects or enhancing effects on Me2SO-induced FLC hemopoietic differentiation. In conclusion, the present study shows that copper complexes of pyridoxal thiosemicarbazone exert action of inducing agent and are able to enhance Me2SO-induced FLC hemopoietic differentiation.
Assuntos
Leucemia Eritroblástica Aguda/patologia , Piridoxal/análogos & derivados , Tiossemicarbazonas/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Eritropoese/efeitos dos fármacos , Vírus da Leucemia Murina de Friend , Hematopoese/efeitos dos fármacos , Camundongos , Piridoxal/farmacologia , Estimulação Química , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/patologiaRESUMO
Three polymorphic forms of 1-methyl-2-nitro-5-vinylimidazole, a potential antimicrobial drug, have been isolated and characterized by thermomicroscopy, differential scanning calorimetry, infrared spectroscopy and X-ray powder diffraction. On the basis of some infrared bands, the hypothesis has been made that the different packing of forms I and II was due to the existence of the molecule in two different conformations in the two forms. The direct confirmation of the hypothesis has been sought by X-ray diffraction of single crystals, but a suitable crystal was obtained only for form II. Form II is orthorhombic, space group Pbca, with unit-cell dimensions: a = 13.05, b = 10.83, c = 10.21 A; Z = 8. From the X-ray analysis, carried out by direct methods, the molecule is planar and the vinyl group is cisoid to the heterocyclic CH group. Then, the existence of the molecule as transoid conformation in form I still remains a hypothesis.
Assuntos
Imidazóis/isolamento & purificação , Varredura Diferencial de Calorimetria/métodos , Cristalização , Espectrofotometria Infravermelho/métodos , Difração de Raios X/métodosRESUMO
As part of a research programme aimed at the synthesis of compounds with antiviral, antibacterial and antitumor properties and their spectroscopic characterization, new thiosemicarbazones deriving from natural aldehydes have been investigated. These substances contain in the same molecule both a chain with nucleophilic centres N, S with tubercolostatic activity, and a glycosidic or alkyl moiety (modified glycosides and nucleosides have recently received a great deal of attention in the fields of neoplastic diseases and viral infections). In this paper the synthesis and the characterization of these compounds by means of 1H NMR, IR, and MS techniques is reported. Biological studies have involved both inhibition of cell proliferation and apoptosis tests on human leukemia cell line U937.