Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 15 de 15
Filtrar
Mais filtros











Intervalo de ano de publicação
1.
J Inorg Biochem ; 240: 112091, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36527994

RESUMO

Gallium and indium octahedral complexes with isoniazid derivative ligands were successfully prepared. The ligands, isonicotinoyl benzoylacetone (H2L1) and 4-chlorobenzoylacetone isonicotinoyl hydrazone (H2L2), and their respective coordination compounds with gallium and indium [GaL1(HL1)] (GaL1), [GaL2(HL2)] (GaL2), [InL1(HL1)] (InL1) and [InL2(HL2)] (InL2) were investigated by NMR, ESI-MS, UV-Vis, IR, single-crystal X-ray diffraction and elemental analysis. In vitro interaction studies with human serum albumin (HSA) evidenced a moderate affinity of all complexes with HSA through spontaneous hydrophobic interactions. The greatest suppression of HSA fluorescence was caused by GaL2 and InL2, which was associated to the higher lipophilicity of H2L2. In vitro interaction studies with CT-DNA indicated weak interactions of the biomolecule with all complexes. Cytotoxicity assays with MCF-7 (breast carcinoma), PC-3 (prostate carcinoma) and RWPE-1 (healthy human prostate epithelial) cell lines showed that complexes with H2L2 are more active and selective against MCF-7, with the greatest cytotoxicity observed for InL2 (IC50 = 10.34 ± 1.69 µM). H2L1 and H2L2 were labelled with gallium-67, and it was verified that 67GaL2 has a greater lipophilicity than 67GaL1, as well as higher stability in human serum or in the presence of apo-transferrin. Cellular uptake assays with 67GaL1 and 67GaL2 evidenced that the H2L2-containing radiocomplex has a higher accumulation in MCF-7 and PC-3 cells than the non-halogenated congener 67GaL1. The anti-Mycobacterium tuberculosis assays revealed that both ligands and metal complexes are potent growth inhibitors, with MIC90 (µg mL-1) values observed from 0.419 ± 0.05 to 1.378 ± 0.21.


Assuntos
Antineoplásicos , Complexos de Coordenação , Gálio , Mycobacterium tuberculosis , Neoplasias , Tuberculose , Masculino , Humanos , Isoniazida/farmacologia , Índio/farmacologia , Gálio/farmacologia , Gálio/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Ligantes , Antineoplásicos/farmacologia , Antineoplásicos/química
2.
Sci Rep ; 11(1): 20562, 2021 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-34663831

RESUMO

Claustral foundation of nests by Atta sexdens Forel (Hymenoptera: Formicidae) involves great effort by its queens, solely responsible for the cultivation of the fungus and care for her offspring at this stage. The minimum workers, after 4 months, open access to the external environment to foraging plants to cultivate the symbiotic fungus, which decomposes the plant fragments and produces gongilidea nodules as food for the individuals in the colony. Colony gas exchange and decomposition of organic matter in underground ant nests generate carbon dioxide (CO2) emitted into the atmosphere. We described the carbon dioxide concentration in colonies in the field. The objective was to evaluate the carbon dioxide concentration in initial A. sexdens colonies, in the field, and their development. The CO2 level was also measured in 4-month-old colonies in the field, using an open respirometric system fitted with an atmospheric air inlet. The CO2 level of the respirometric container was read by introducing a tube into the nest inlet hole and the air sucked by a peristaltic pump into the CO2 meter box. The CO2 concentration in the initial colony was also measured after 4 months of age, when the offspring production (number of eggs, larvae, pupae and adult workers) stabilized. Ten perforations (15 cm deep) was carried out in the adjacent soil, without a nest of ants nearby, to determine the concentration of CO2. The composition of the nests in the field was evaluated after excavating them using a gardening shovel and they were stored in 250 ml pots with 1 cm of moistened plaster at the bottom. The CO2 concentration was higher in field nest than in adjacent soil. The concentration of carbon dioxide in A. sexdens nests in the field is higher than in those in the soil, due to the production of CO2 by the fungus garden and colony.


Assuntos
Dióxido de Carbono/análise , Fungos/metabolismo , Comportamento de Nidação/fisiologia , Animais , Formigas/metabolismo , Formigas/microbiologia , Comportamento Animal , Fungos/química , Simbiose/fisiologia
3.
Neotrop. ichthyol ; 19(4): e210056, 2021. tab, ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-1351150

RESUMO

Moenkhausia is a highly specious genus among the Characidae, composed of 96 valid species. Only twelve species have a known karyotype. Thus, here are presented the first cytogenetic data of two allopatric populations of Moenkhausia bonita and one of M. forestii, both belonging to the upper Paraná River basin (PR) with discussion on the evolutionary and cytotaxonomic aspects of the genus. The two species presented 2n = 50 chromosomes but different karyotype formulas and occurrence of 1-2 B chromosomes. These elements are small metacentrics in M. bonita and small acrocentrics in M. forestii. In both species, B chromosomes were euchromatic. Ag-NOR sites were found in pair 3 (metacentric), coinciding with fluorescent in situ hybridization (FISH) by the 18S rDNA probe in both species. However, the species differed in terms of the number and position of 5S rDNA sites. Heterochromatic blocks, mapped in M. bonita showed the least amount of heterochromatin in the terminal and pericentromeric regions, while the M. forestii karyotype revealed a greater amount of interstitial heterochromatic blocks. The karyotype distinctions between the two species, including the morphology of B chromosomes, may contribute as a reference in the taxonomic studies in this group.(AU)


Moenkhausia é um gênero altamente especioso dentre os Characidae, composto por 96 espécies válidas, mas apenas doze espécies têm seus cariótipos conhecidos. Portanto, são apresentados aqui os primeiros dados citogenéticos de duas populações alopátricas de Moenkhausia bonita e uma de M. forestii, ambas pertencentes à bacia do alto rio Paraná (PR), com uma ampla discussão sobre os aspectos evolutivos e citotaxonômicos do gênero. As duas espécies apresentaram 2n = 50 cromossomos, mas diferentes fórmulas cariotípicas e ocorrência de 1-2 cromossomos B. Esses elementos são pequenos metacêntricos em M. bonita e acrocêntricos pequenos em M. forestii. Em ambas as espécies, os cromossomos B apresentaram-se eucromáticos. Sítios Ag-NOR foram encontrados no par 3 (metacêntrico), coincidindo com a hibridização fluorescente in situ (FISH) pela sonda 18S rDNA em ambas as espécies. No entanto, as espécies diferiram em termos de número e posição dos sítios de 5S rDNA. Blocos heterocromáticos mapeados em M. bonita revelaram pequena quantidade de heterocromatina nas regiões terminal e pericentromérica, enquanto o cariótipo de M. forestii revelou uma maior quantidade de blocos heterocromáticos intersticiais. As distinções cariotípicas entre as duas espécies, incluindo a morfologia dos cromossomos B, podem contribuir como uma referência em estudos taxonômicos neste grupo.(AU)


Assuntos
Animais , Heterocromatina , Cromossomos , Citogenética , Characidae , Hibridização in Situ Fluorescente
4.
Inorg Chem ; 59(13): 9261-9269, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32543836

RESUMO

Tetraphenylphosphonium salts of Co and Fe complexes with alkyl-substituted, tert-butyl (tb), and isopropyl (dp) 2,3-thiophenedithiolate (α-tpdt) ligands, namely, TPP[Co(α-tb-tpdt)2] (3), TPP2[Fe(α-tb-tpdt)2]2 (4a-b), TPP[Co(α-dp-tpdt)2] (5), and TPP[Fe(α-dp-tpdt)2] (6) were prepared and characterized by cyclic voltammetry, single crystal X-ray diffraction, magnetic susceptibility measurements, and 57Fe Mössbauer spectroscopy. Compound 3 and 5 are isostructural with their Au and Ni analogues with a square-planar coordination geometry. Compound 4 presents two polymorphs (4a-b) both showing a Fe(III) bisdithiolene dimerization. The magnetic susceptibility of 3 and 5 exhibits behavior dominated by antiferromagnetic interactions, with room-temperature magnetic moments of 3.40 and 3.36 µB, respectively, indicating that these square-planar Co(III) complexes assume an intermediate spin electronic configuration (S = 1) as supported by multiconfigurational and DFT calculations.

5.
J Inorg Biochem ; 202: 110904, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31671298

RESUMO

The emergence of resistance to antimicrobial and anticancer drugs poses severe threats to public health worldwide, highlighting the need for more efficient treatments. Here, four monoanionic Au bisdithiolate complexes [Au(mnt)2]- (where mnt = 1,1-dicyanoethylene-2,2-dithiolate)(1), [Au(i-mnt)2]- (where i-mnt = 2,2-dicyanoethylene-1,1-dithiolate)(2), [Au(cdc)2]- (where cdc = cyanodithioimido carbonate)(3), and [Au(qdt)2]- (where qdt = quinoxaline-2,3-dithiolate)(4) were screened for their antimicrobial and antitumor activities. Complexes 3 and 4 showed antibacterial activity against Staphylococcus aureus [minimal inhibitory concentration (MIC) = 15.3 and 14.7 µg/mL, respectively]. Complex 3 also caused significant growth inhibition of Candida glabrata (MIC = 7.0 µg/mL). Concentrations of complexes 1-4 up to 125 µg/mL had no growth inhibition activity against Escherichia coli. The cytotoxic activity of complexes 1-4 was evaluated against the ovarian cancer cells A2780 and A2780cisR, sensitive and resistant to cisplatin, respectively. All compounds showed high cytotoxic activities against both tumoral cell lines, exhibiting IC50 values in the low micromolar range (0.9-5.5 µM) upon 48 h incubation. In contrast to complex 1, the complexes 2-4 induced a dose-dependent formation of reactive oxygen species (ROS), similar to the observed for the reference drugs auranofin and cisplatin. Opposite to 4, complexes 1-3 were able to activate caspase 3/7, suggesting the involvement of apoptosis in the mechanism of cell death. Contrasting with cisplatin, complexes 3, 4 and auranofin did not cause DNA damage. Combined, these data provide evidence that these monoanionic gold bisdithiolates, particularly complex 3, are potential lead compounds to further explore as therapeutic drugs.


Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Ouro/química , Compostos Organometálicos/farmacologia , Compostos de Sulfidrila/química , Anti-Infecciosos/química , Antineoplásicos/química , Apoptose , Candida glabrata/efeitos dos fármacos , Caspase 3/metabolismo , Cisplatino/farmacologia , Escherichia coli/efeitos dos fármacos , Feminino , Humanos , Testes de Sensibilidade Microbiana , Compostos Organometálicos/química , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Staphylococcus aureus/efeitos dos fármacos
6.
Molecules ; 23(2)2018 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-29443956

RESUMO

Gold and nickel bisdithiolene complexes with methyl and tert-butyl substituted thiophenetetrathiafulavalenedithiolate ligands (α-mtdt and α-tbtdt) were prepared and characterized. These complexes were obtained, under anaerobic conditions, as tetrabutylammonium salts. The diamagnetic gold monoanion (n-Bu4N)[Au(α-mtdt)2] (3) and nickel dianionic species (n-Bu4N)x[Ni(α-mtdt)2] (x = 1,2) (4) were similar to the related non-substituted extended thiophenic-TTF (TTF = tetrathiafulvalene) bisdithiolenes. However the introduction of the large, bulky substituent tert-butyl, led to the formation of a Au (I) dinuclear complex, (n-Bu4N)2[Au2(α-tbtdt)2] (5). The neutral methyl substituted gold and nickel complexes were easily obtained through air or iodine exposure as polycrystalline or amorphous fine powder. [Au(α-mtdt)2] (6) and [Ni(α-mtdt)2] (7) polycrystalline samples display properties of a metallic system with a room temperature electrical conductivity of 0.32 S/cm and ≈4 S/cm and a thermoelectric power of ≈5 µV/K and ≈32 µV/K, respectively. While [Au(α-mtdt)2] (6) presented a Pauli-like magnetic susceptibility typical of conducting systems, in [Ni(α-mtdt)2] (7) large magnetic susceptibilities indicative of high spin states were observed. Both electric transport properties and magnetic properties for gold and nickel [M(α-mtdt)2] are indicative that these compounds are single component molecular conductors.


Assuntos
Complexos de Coordenação/química , Ouro/química , Níquel/química , Tiofenos/química , Cristalografia por Raios X , Ligantes , Modelos Moleculares , Compostos Organometálicos/química
7.
J Inorg Biochem ; 160: 275-86, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27267415

RESUMO

The formation of quadruple-stranded DNA induced by planar metal complexes has particular interest in the development of novel anticancer drugs. This is especially relevant for the inhibition of telomerase, which plays an essential role in cancer cell immortalization and is overexpressed in ca. 85-90% of cancer cells. Moreover, G-quadruplexes also exist in other locations in the human genome, namely oncogene promoter regions, and it has been hypothesized that they play a regulatory role in gene transcription. Herein we report a series of new anthracene-containing terpyridine ligands and the corresponding Cu(II) and Pt(II) complexes, with different linkers between the anthracenyl moiety and the terpyridine chelating unit. The interaction of these ligands and metal complexes with different topologies of DNA was studied by several biophysical techniques. The Pt(II) and Cu(II) complexes tested showed affinity for quadruplex-forming sequences with a good selectivity over duplex DNA. Importantly, the free ligands do not have significant affinity for any of the DNA sequences used, which shows that the presence of the metal is essential for high affinity (and selectivity). This effect is more evident in the case of the Pt(II) complexes. Moreover, the presence of a longer linker between the chelating terpyridine unit and the anthracene moiety enhances the interaction with G-quadruplex-forming sequences. We further evaluated the ability of the Cu(II) complexes to interact with, and stabilize G-quadruplex containing regions in oncogene promoters via a polymerase stop assay. These studies indicated that the metal complexes are able to induce G-quadruplex formation and stop polymerase activity.


Assuntos
Antracenos/química , Antineoplásicos/química , Complexos de Coordenação/química , Proteínas Proto-Oncogênicas c-myc/metabolismo , Piridinas/química , Antineoplásicos/síntese química , Sítios de Ligação , Cátions Bivalentes , Complexos de Coordenação/síntese química , Cobre/química , Cristalografia por Raios X , Transferência Ressonante de Energia de Fluorescência , Expressão Gênica , Humanos , Oligonucleotídeos/química , Platina/química , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/genética , Soluções
8.
Inorg Chem ; 52(7): 3845-50, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-23517057

RESUMO

We report the synthesis of the iron(III) complex of the hexadentate Schiff base ligand nsal2trien obtained from the condensation of triethylenetetramine and 2 equiv. of 2-hydroxy-1-naphthaldehyde. The study of the salt [Fe(nsal2trien)]SCN (1) by magnetic susceptibility measurements and Mössbauer spectroscopy reveals a rather unique behavior that displays thermally induced spin crossover (SCO) with two well-separated steps at 250 (gradual transition) and 142 K (steep transition). Single crystal X-ray structures were obtained at 294, 150, and 50 K, for the high spin (HS), intermediate (Int), and low spin (LS) phases. The HS and LS phases are isostructural, and based on a single Fe(III) site (either HS or LS) an unusual symmetry break occurs in the transition to the Int ordered phase, where the unit cell includes two distinct Fe(III) sites and is based on a repetition of the [HS-LS] motif. The two-step SCO behavior of 1 must result from the existence of structural constraints preventing the full conversion HS ↔ LS in a single step.

9.
J Inorg Biochem ; 105(5): 637-44, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21450266

RESUMO

Tridentate pyrazole-containing ligands of the Schiff base type, SalPz - HL(1), Cl(2)SalPz - HL(2) and I(2)SalPz - HL(3), were used to prepare a series of new Cu(II) complexes (CuSalPz - 1, CuCl(2)SalPz - 2 and CuI(2)SalPz - 3). These new complexes have been studied by different analytical techniques (electrospray ionization mass spectrometry (ESI-MS), elemental analysis, FT-IR and EPR). The spectroscopic properties of 1-3 are consistent with the formation of Cu(II) complexes coordinated by monoanionic and tridentate (N,N,O)-chelators, behaving as monomeric species in aqueous solution, as shown by EPR studies. Crystals of 2 and 3, obtained by slow concentration of methanolic solutions of the compounds, were also analyzed by X-ray diffraction analysis. The X-ray structural study has shown that 2 crystallized as a dinuclear compound, [Cu(2)(µ-Cl)(2)(Cl(2)SalPz)(2)], while the solid state structure determined for 3 is best described by monomeric units of [CuCl(I(2)SalPz)] displaying short Cu···Cl intermolecular contacts. The in vitro evaluation of 1-3 comprised the study of their DNA-cleaving ability using plasmid DNA and the assessment of their cytotoxic activity against several human cancer cell lines (PC-3 prostate, MCF-7 breast and A2780 and A2780cisR-ovary). The studies with plasmid DNA have shown that 2 and 3 induce extensive DNA cleavage in the presence of different additives. The cytotoxic activity of 2 and 3 is comparable to the one presented by cisplatin, with the exception of the A2780 cell line where cisplatin is more active. It has been found that the introduction of halogen substituents in the phenolate rings of the chelators enhanced the cytotoxicity of the respective Cu(II) complexes.


Assuntos
Quelantes/síntese química , Quelantes/toxicidade , Complexos de Coordenação/síntese química , Cobre/química , Clivagem do DNA , DNA/química , Pirazóis/química , Linhagem Celular Tumoral , Quelantes/química , Complexos de Coordenação/química , Complexos de Coordenação/toxicidade , Cobre/metabolismo , Cristalografia por Raios X , DNA/metabolismo , Humanos , Ligantes , Pirazóis/síntese química , Bases de Schiff/química , Espectrometria de Massas por Ionização por Electrospray
10.
Neotrop. ichthyol ; 9(1): 177-182, Mar. 2011. ilus
Artigo em Inglês | LILACS | ID: lil-583966

RESUMO

Este estudo apresenta dados cromossômicos de Megalonema platanum do rio Tibagi, Paraná, Brasil e do rio Paraná, Argentina. O número diploide foi igual 54 com composição cariotípica de 24m+16sm+2st+12a em ambas populações. Os sítios AgNORs foram detectados na posição terminal de um par submetacêntrico das duas populações analisadas, coincidindo com constrição secundária no braço curto do par 15. CMA3 e FISH com sonda de DNAr 18S exibiram sinais fluorescentes que correspondem aos sítios AgNORs e à constrição secundária. A presença de um pequeno cromossomo supranumerário acrocêntrico foi observado em M. platanum do rio Tibagi, com heterocromatina centromérica. Outros blocos heterocromáticos foram evidenciados na posição terminal de alguns cromossomos e um par cromossômico submetacêntrico grande, provavelmente o primeiro par, mostrou heterocromatina intersticial. Na população do rio Paraná foram observados ainda blocos heterocromáticos em ambas regiões terminais em alguns cromossomos. Este trabalho mostra pela primeira vez dados citogenéticos de M. platanum, que é uma espécie muito rara na bacia do rio Paraná e pode estar ameaçada de extinção.


This study presents chromosomal data of Megalonema platanum from rio Tibagi, Paraná, Brazil and from rio Paraná, Argentina. The diploid number was equal 54 with karyotype composition of 24m+16sm+2st+12a in both populations. The AgNOR siteswere detected in the terminal position of a submetacentric pair of the two analyzed populations, coinciding with secondary constrictions on the short arm of pair 15. CMA3 and FISH with 18S rDNA probe displayed fluorescent signals that correspond to the AgNOR sites and secondary constriction. The presence of a small acrocentric supernumerary chromosome can be observed in M. platanum from rio Tibagi, with centromeric heterochromatin. Others heterochromatic blocks were evidenced in the terminal position of some chromosome and one metacentric large chromosome pair, probably the first pair, showed an interstitial heterochromatin. In the population of the rio Paraná were still observed heterochromatic blocks in both ends in some chromosomes. This work brings for the first time cytogenetic date of M. platanum, which is a very rare species in the rio Paraná basin and may be endangered.


Assuntos
Animais , Citogenética/métodos , Cromossomos/genética , Peixes/classificação
11.
Metallomics ; 2(8): 571-80, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21072342

RESUMO

Following previous studies with a DOTA-like bifunctional chelator (H(3)L1) containing an ethylenic linker between the macrocycle backbone and a quinazoline pharmacophore, we synthesized and fully characterized a congener macrocyclic ligand (H(3)L2) having a longer, five-carbon spacer for the linkage of the quinazoline moiety. Both H(3)L1 and H(3)L2 were used to prepare indium(III) complexes aiming at their evaluation as radioactive probes for in vivo targeting of EGFR-TK. The protonation constants (log K(Hi)) of H(3)L2 were determined by potentiometry and UV-Vis spectrophotometry and the values found are 12.18, 9.74, 4.99, 3.91 and 2.53. The stability and protonation constants of InL (L = L1, L2) were also obtained from a combined potentiometry and UV-VIS spectrophotometry study. The reaction of InCl(3) with H(3)L1 and H(3)L2 led to the formation of the well-defined complexes InL1 and InL2, containing In(iii) ions coordinated by a seven (N(4),O(3)) donor atom set. These new complexes were fully characterized by spectroscopic methods (IR, NMR, ESI-MS), HPLC and by X-ray diffraction analysis in the case of InL1. The radioactive congener (111)InL2 was prepared from the reaction of (111)In-chloride with H(3)L2, in high yield and high radiochemical purity. (111)InL2 is a neutral complex that presents a hydrophilic character and exhibits a high in vitro and in vivo stability. H(3)L2 and InL2 do not inhibit the cell growth of A431 cervical carcinoma cells. In this EGFR-expressing cell line, (111)InL2 has shown very low cell internalization. These findings indicate that these DOTA-like chelators are not the best suited bifunctional ligands to obtain In(iii) complexes with adequate biological properties for targeting the EGFR-TK.


Assuntos
Quelantes/química , Compostos Heterocíclicos com 1 Anel/química , Índio/química , Índio/farmacologia , Quinazolinas/química , Animais , Linhagem Celular , Cromatografia Líquida de Alta Pressão , Cristalografia por Raios X , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Índio/farmacocinética , Espectroscopia de Ressonância Magnética , Camundongos , Potenciometria , Espectrofotometria Infravermelho , Espectrofotometria Ultravioleta , Distribuição Tecidual
12.
Biol. Res ; 42(3): 289-296, 2009. ilus
Artigo em Inglês | LILACS | ID: lil-531962

RESUMO

Karyotypes of seventeen Hoplias malabaricus specimens, collected in the fish culture station of UNOPAR (University of Northern Paraná), were analyzed. The station is in the Claro River system in the Tibagi River basin. Two distinct and coexistent karyotype forms (cytotypes) were identified, comprising either 42 chromosomes (cytotype A) or 40 chromosomes (cytotype C), both presenting metacentric and submetacentric chromosomes. In two specimens, one male and one female, it was not possible to characterize a modal diploid number because different cell lines were observed, with a predominance of 2n=41 and 2n=42 chromosomes at a frequency of 38.24 percent and 41.12 percent, respectively. The karyotype with 2n=41 showed some putative monosomic and trisomic chromosomes, while the karyotype with 2n=42 showed 21 chromosomal pairs, similar to cytotype A. RAPD analysis showed that these two specimens have the same band pro file of cytotype A (Nei's genetic identity=92 percent), discarding a possible hybridization between both cytotypes and supporting the mosaicism hypothesis. These findings corroborate the isolation between cytotypes A and C.


Assuntos
Animais , Feminino , Masculino , Peixes/genética , Mosaicismo/veterinária , Cariotipagem , Técnica de Amplificação ao Acaso de DNA Polimórfico
13.
Dalton Trans ; (24): 3215-25, 2008 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-18688420

RESUMO

The quinazoline derivatives (3-chloro-4-fluorophenyl)quinazoline-4,6-diamine (2) and (3-bromophenyl)quinazoline-4,6-diamine (3) were labelled with (99m)Tc using the "4 + 1" mixed-ligand system [Tc(NS3)(CN-R)] and the tricarbonyl moiety fac-[Tc(CO)3]+. In the "4 + 1" approach the technetium(iii) is stabilized by a monodentate isocyanide bearing a quinazoline fragment (L1,L2 ) and by the tetradentate tripodal ligand tris(2-mercaptoethyl)-amine (NS3). In the "4 + 1" approach, 99mTc-labelling was performed in a two-step procedure, the complexes [Tc(NS3)(L1)] (7a) and [Tc(NS3)(L2)] (8a) being obtained in about 50-70% yield. In the tricarbonyl approach, the fac-[Tc(CO)3]+ unit is anchored by two different monoanionic chelators bearing the quinazoline derivatives (3-chloro-4-fluorophenyl)quinazoline-4,6-diamine (2) and (3-bromophenyl)quinazoline-4,6-diamine (3). Both chelators have a N2O donor atom set, but one contains a pyrazolyl ring (L5H) and the other contains a pyridine unit (L6H). In both cases the conjugation of the quinazoline to the chelator was done through the secondary amine of the potentially tridentate and monoanionic chelators, the corresponding 99mTc-complexes (10a, 11a) being obtained in quantitative yield. The identities of the 99mTc-labelled quinazolines (7a, 8a, 10a, 11a) were confirmed by comparison with the HPLC profiles of the analogous Re compounds (7, 8, 10, 11). All these Re complexes were characterized by NMR and IR spectroscopy, elemental analysis and in some cases by MS and X-ray diffraction analysis. In vitro studies indicate that the quinazoline fragments, after conjugation to the cyano group (L1, L2) or to the pyrazolyl containing chelator (L5H), as well as the corresponding Re complexes (7, 8, 10) inhibit significantly the EGFR autophosphorylation and also inhibit A431 cell growth. These two effects were also found for the pyridine-containing chelator (L6H) and corresponding Re complex (11), although to a lesser extent.


Assuntos
Biomarcadores/metabolismo , Receptores ErbB/metabolismo , Compostos de Organotecnécio/química , Quinazolinas/química , Rênio/química , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Proliferação de Células/efeitos dos fármacos , Quelantes , Cromatografia Líquida de Alta Pressão , Cristalografia por Raios X , Fator de Crescimento Epidérmico/farmacologia , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Compostos de Organotecnécio/síntese química , Compostos de Organotecnécio/farmacologia , Fosforilação/efeitos dos fármacos , Células Tumorais Cultivadas
14.
Inorg Chem ; 43(12): 3631-41, 2004 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-15180417

RESUMO

The deprotonated form of the pyrazine-2,3-diselenol (pds) ligand, pds(2-), reacts with Ni(II) inorganic salts to form the nickel compounds [Ni(II)(pds)(2)](nBu(4)N)(2) (1), [Ni(II)(pds)(2)]Na(2).2H(2)O (2), and [Ni(III)(pds)(2)](2)Na(2).4H(2)O (3), depending on the reaction conditions. They are characterized by NMR, EPR, UV-vis, and IR spectroscopies, elemental analysis, cyclic voltammetry, and X-ray crystallography. The crystal structure of compound 3 shows the formation of segregated stacks of Ni(pds)(2-) units, with a strong dimerization along the stacks. The stacked fashion of the crystal packing was expected since the supramolecular forces of the alkaline side coordination to the pyrazine moieties dominate, as happens in the recently reported analogous copper system [Cu(III)(pds)(2)]Na.2H(2)O. The structure of 2 further emphasizes the alkaline coordination as the dominating supramolecular event, and an orthogonal array of 2D layers is observed. The absence of alkaline cations in complex 1 is reflected in a crystal packing with isolated complex Ni(pds)(2)(2-) units. The dimerization found in the paramagnetic Ni(III) complex 3 promotes a very strong antiferromagnetic interaction, leading to a singlet ground state.

15.
Arq. neuropsiquiatr ; 56(1): 32-8, mar. 1998. tab
Artigo em Inglês | LILACS | ID: lil-212439

RESUMO

Purpose: To assess public awareness and attitudes toward epilepsy in Brazilians of different cultural and socioeconomic backgrounds. Background: Several studies have examined public awareness and attitudes toward epilepsy in various countries but there are no equivalent data for Brazil or South America. Material and Methods: We have applied the survery proposed by Caveness and Gallup, with some modifications and adaptations to four groups (I-IV) of subjects: I-105 individuals accompanying patients to the Ophthalmologic outpatient clinic of the Hospital das Clínicas of the State University of Campinas (UNICAMP); II-93 students recently admitted to medical and nursing school; III- 101 senior non-medical students; and IV- 69 senior medical students. Groups II, III, and IV were students at UNICAMP. Results: Individuals with a low socioeconomic standing had a poor profile of familiarity, knowledge and attitudes toward epilepsy. The pre-university and university students had a relatively good profile when compared to the published international polls. Senior medical students had an excellent level of familiarity and knowledge, but showed no change in their objection to having a son or a daughter marry an epileptic person. Conclusions: Our data suggest that there is a clear-cut relationship between the level of education and the individual's familiarity and atitudes toward epilepsy. Effective elimination of the prejudice toward epilepsy requires specific training and not just general, superficial information about the condition.


Assuntos
Adulto , Pessoa de Meia-Idade , Feminino , Humanos , Adolescente , Conscientização , Epilepsia/psicologia , Conhecimentos, Atitudes e Prática em Saúde , Preconceito , Idoso de 80 Anos ou mais , Brasil , Escolaridade , Fatores Socioeconômicos , Inquéritos e Questionários
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA