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1.
Chem Commun (Camb) ; 56(20): 3065-3068, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32049076

RESUMO

Herein, a novel stacked hexagonal prism, Ag@Ni-MOF-1, was designed and developed as an integrated SERS platform not only for successfully catalyzing the in situ synthesis of DA-quinone under physiological pH, but also for establishing an approach for specific determination of Cys, an important species in the brain related to Alzheimer's disease (AD).


Assuntos
Benzoquinonas/síntese química , Materiais Biomiméticos/química , Dopamina/síntese química , Níquel/química , Compostos Organometálicos/química , Prata/química , Benzoquinonas/química , Catálise , Cisteína/análise , Dopamina/química , Humanos , Concentração de Íons de Hidrogênio , Compostos Organometálicos/síntese química , Análise Espectral Raman
2.
Molecules ; 25(2)2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31936557

RESUMO

Synthesis of new chromium(II) complexes with chelating bis(alkoxide) ligand [OO]Ph (H2[OO]Ph = [1,1':4',1''-terphenyl]-2,2''-diylbis(diphenylmethanol)) and their subsequent reactivity in the context of catalytic production of carbodiimides from azides and isocyanides are described. Two different Cr(II) complexes are obtained, as a function of the crystallization solvent: mononuclear Cr[OO]Ph(THF)2 (in toluene/THF, THF = tetrahydrofuran) and dinuclear Cr2([OO]Ph)2 (in CH2Cl2/THF). The electronic structure and bonding in Cr[OO]Ph(THF)2 were probed by density functional theory calculations. Isolated Cr2([OO]Ph)2 undergoes facile reaction with 4-MeC6H4N3, 4-MeOC6H4N3, or 3,5-Me2C6H3N3 to yield diamagnetic Cr(VI) bis(imido) complexes; a structure of Cr[OO]Ph(N(4-MeC6H4))2 was confirmed by X-ray crystallography. The reaction of Cr2([OO]Ph)2 with bulkier azides N3R (MesN3, AdN3) forms paramagnetic products, formulated as Cr[OO]Ph(NR). The attempted formation of a Cr-alkylidene complex (using N2CPh2) instead forms chromium(VI) bis(diphenylmethylenehydrazido) complex Cr[OO]Ph(NNCPh2)2. Catalytic formation of carbodiimides was investigated for the azide/isocyanide mixtures containing various aryl azides and isocyanides. The formation of carbodiimides was found to depend on the nature of organoazide: whereas bulky mesitylazide led to the formation of carbodiimides with all isocyanides, no carbodiimide formation was observed for 3,5-dimethylphenylazide or 4-methylphenylazide. Treatment of Cr2([OO]Ph)2 or H2[OO]Ph with NO+ leads to the formation of [1,2-b]-dihydroindenofluorene, likely obtained via carbocation-mediated cyclization of the ligand.


Assuntos
Quelantes/química , Cromo/química , Compostos Organometálicos/química , Alcanos/química , Azidas/química , Catálise , Quelantes/síntese química , Cristalografia por Raios X , Ligantes , Estrutura Molecular , Compostos Organometálicos/síntese química
4.
Molecules ; 25(2)2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31936003

RESUMO

: A series of free base and Zn(II) phthalocyanines featuring fluorenyl antennae linked by methoxy or oxo bridges to the phthalocyanine core (Pc) were synthesized and characterized. Selected linear and nonlinear (two-photon absorption) optical properties of these new compounds were subsequently studied. As previously observed for related porphyrin dendrimers bearing 2-fluorenyl peripheral dendrons, an efficient energy transfer occurs from the peripheral antennae to the central phthalocyanine core following excitation in the fluorenyl-based π-π* absorption band of these chromophores. Once excited, these compounds relax to the ground state, mostly by emitting intense red light or by undergoing intersystem crossing. As a result, the tetrafunctionalized Zn(II) phthalocyanines are fluorescent, but can also efficiently photosensitize molecular oxygen in tetrahydrofurane (THF), forming singlet oxygen with nearly comparable yields to bare Zn(II) phthalocyanine (ZnPc). In comparison with the latter complex, the positive role of the fluorenyl-containing antennae on one- and two-photon brightness (2PA) is presently demonstrated when appended in peripheral (ß) position to the phthalocyanine core. Furthermore, when compared to known porphyrin analogues, the interest in replacing the porphyrin by a phthalocyanine as the central core to obtain more fluorescent two-photon oxygen photosensitizers is clearly established. As such, this contribution paves the way for the future development of innovative biphotonic photosensitizers usable in theranostics.


Assuntos
Fluorenos/química , Indóis/química , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/química , Transferência de Energia , Fluorenos/síntese química , Indóis/síntese química , Luz , Luminescência , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Fótons , Porfirinas/química , Oxigênio Singlete/isolamento & purificação , Análise Espectral
5.
Chemistry ; 26(8): 1697, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31922634

RESUMO

Invited for the cover of this issue is the group of Torres at the University of Madrid. The image of the cover of this issue depicts cancer cells being destroyed by reactive singlet oxygen produced by ruthenium phthalocyanine glycoconjugates under red light. The work, developed at the Universities of Madrid, Aveiro, Lisbon and Coimbra, describes ruthenium phthalocyanines as powerful bladder cancer PDT agents. Read the full text of the article at 10.1002/chem.201903546.


Assuntos
Compostos Organometálicos/química , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/metabolismo , Humanos , Compostos Organometálicos/síntese química , Compostos Organometálicos/uso terapêutico , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico
6.
Chemistry ; 26(8): 1789-1799, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-31605633

RESUMO

The synthesis of ruthenium(II) phthalocyanines (RuPcs) endowed with one carbohydrate unit-that is, glucose, galactose and mannose-and a dimethylsulfoxide (DMSO) ligand at the two axial coordination sites, respectively, is described. Two series of compounds, one unsubstituted at the periphery, and the other one bearing eight PEG chains at the isoindole meta-positions, have been prepared. The presence of the axial DMSO unit significantly increases the phthalocyanine singlet oxygen quantum yields, related to other comparable RuPcs. The compounds have been evaluated for PDT treatment in bladder cancer cells. In vitro studies have revealed high phototoxicity for RuPcs unsubstituted at their periphery. The phototoxicity of PEG-substituted RuPcs has been considerably improved by repeated light irradiation. The choice of the axial carbohydrate introduced little differences in the cellular uptake for both series of photosensitizers, but the phototoxic effects were considerably higher for compounds bearing mannose units.


Assuntos
Compostos Organometálicos/química , Fármacos Fotossensibilizantes/síntese química , Oxigênio Singlete/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Luz , Compostos Organometálicos/síntese química , Compostos Organometálicos/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Espectrofotometria , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/metabolismo
7.
Dalton Trans ; 49(5): 1403-1415, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31851200

RESUMO

The synthesis, characterization and biological activity of six bioorganometallic conjugates of ciprofloxacin with ferrocenyl, ruthenocenyl and cymantrenyl entities are described. Their antimicrobial activities were investigated against Gram-positive bacteria, Gram-negative bacteria and bloodstream forms of Trypanosoma brucei. Furthermore, the morphological changes of bacterial cells upon treatment with the conjugates were examined by scanning electron microscopy. In addition, the cytotoxicity of the conjugates against tumor and normal mammalian cells was also investigated. The results showed that conjugation of an organometallic moiety can significantly enhance the antimicrobial activity of the antibiotic ciprofloxacin drug. It was found that N-alkyl cymantrenyl and ruthenocenyl ciprofloxacin conjugates were the most effective derivatives although other conjugates also showed significant antimicrobial activity. The increase in the antimicrobial activity was most likely due to two independent mechanisms of action. The first mechanism is due to the bacterial topoisomerase inhibitory activity of ciprofloxacin while the second mechanism can be attributed to the generation of reactive oxygen species caused by the organometallic moiety. The presence of two modes of action enables the conjugates to kill bacteria in their stationary growth phase and to overcome the drug resistance of S. aureus strains. In addition, the conjugates showed promising selectivity toward bacterial and parasitic cells over mammalian cells.


Assuntos
Antibacterianos/farmacologia , Antineoplásicos/farmacologia , Ciprofloxacino/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Compostos Organometálicos/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciprofloxacino/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Relação Estrutura-Atividade
8.
J Enzyme Inhib Med Chem ; 35(1): 59-64, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31663383

RESUMO

A primary strategy to combat antimicrobial resistance is the identification of novel therapeutic targets and anti-infectives with alternative mechanisms of action. The inhibition of the metalloenzymes carbonic anhydrases (CAs, EC 4.2.1.1) from pathogens (bacteria, fungi, and protozoa) was shown to produce an impairment of the microorganism growth and virulence. As phosphonamidates have been recently validated as human α-CA inhibitors (CAIs) and no phosphorus-based zinc-binding group have been assessed to date against ß-class CAs, herein we report an inhibition study with this class of compounds against ß-CAs from pathogenic bacteria, fungi, and protozoa. Our data suggest that phosphonamidates are among the CAIs with the best selectivity for ß-class over human isozymes, making them interesting leads for the development of new anti-infectives.


Assuntos
Amidas/farmacologia , Anti-Infecciosos/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Compostos Organometálicos/farmacologia , Ácidos Fosfóricos/farmacologia , Amidas/química , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Bactérias/efeitos dos fármacos , Bactérias/enzimologia , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Relação Dose-Resposta a Droga , Fungos/efeitos dos fármacos , Fungos/enzimologia , Humanos , Leishmania donovani/efeitos dos fármacos , Leishmania donovani/enzimologia , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Ácidos Fosfóricos/química , Fósforo/química , Fósforo/farmacologia , Relação Estrutura-Atividade , Zinco/química , Zinco/farmacologia
9.
Anticancer Res ; 39(12): 6693-6699, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31810934

RESUMO

BACKGROUND/AIM: Melanoma represents a big challenge for clinical treatment. Besides being the most aggressive and the deadliest form of skin cancer, it is often refractory to commonly used anticancer drugs. Hence, developing new anti-cancer agents is crucial to improve refractory melanoma treatment. Studies using palladium(II) complexes have reported antitumor effects on cancer cells. In this study, we aimed to determine the cytotoxic effect of three novel synthesized Pd(II) complexes with Schiff bases derived from 4-aminoacetophenone on the MDA-MB-435 melanoma cell line. MATERIALS AND METHODS: Cells were treated with ligand and Pd(II) complexes. Cell viability, morphology and death induction upon treatment were examined. RESULTS: Novel synthesized Pd(II) complexes led to decreased viability of cells. They also induced morphological alterations and cell death, mainly in the C3 complex. CONCLUSION: The novel synthesized complexes have a significant cytotoxic effect on cell line MDA-MB-435, especially C3 and can be considered as an antitumor agent for further studies.


Assuntos
Acetofenonas/química , Antineoplásicos/uso terapêutico , Melanoma/tratamento farmacológico , Compostos Organometálicos/uso terapêutico , Paládio/uso terapêutico , Bases de Schiff/uso terapêutico , Neoplasias Cutâneas/tratamento farmacológico , Antineoplásicos/síntese química , Morte Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Técnicas In Vitro , Ligantes , Compostos Organometálicos/síntese química , Paládio/química , Rodaminas , Bases de Schiff/química
10.
Molecules ; 24(21)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671705

RESUMO

A series of new ferrocene- and ruthenocene-containing iridium(III) heteroleptic complexes of the type [(ppy)2Ir(RCOCHCOR')], with ppy = 2-pyridylphenyl, R = Fc = FeII(η5-C5H4)(η5-C5H5) and R' = CH3 (1) or Fc (2), as well as R = Rc = RuII(η5-C5H4)(η5-C5H5) and R' = CH3 (3), Rc (4) or Fc (5) was synthesized via the reaction of appropriate metallocene-containing ß-diketonato ligands with [(ppy)2(-Cl)Ir]2. The single crystal structure of 3 (monoclinic, P21/n, Z = 4) is described. Complexes 1-5 absorb light strongly in the region 280-480 nm the metallocenyl -diketonato substituents quench phosphorescence in 1-5. Cyclic and square wave voltammetric studies in CH2Cl2/[N(nBu)4][B(C6F5)4] allowed observation of a reversible IrIII/IV redox couple as well as well-resolved ferrocenyl (Fc) and ruthenocenyl (Rc) one-electron transfer steps in 1-5. The sequence of redox events is in the order Fc oxidation, then IrIII oxidation and finally ruthenocene oxidation, all in one-electron transfer steps. Generation of IrIV quenched phosphorescence in 6, [(ppy)2Ir(H3CCOCHCOCH3)]. This study made it possible to predict the IrIII/IV formal reduction potential from Gordy scale group electronegativities, χR and/or ΣχR' of -diketonato pendent side groups as well as from DFT-calculated energies of the highest occupied molecular orbital of the species involved in the IrIII/IV oxidation at a 98 % accuracy level.


Assuntos
Teoria da Densidade Funcional , Eletroquímica , Compostos Organometálicos/química , Compostos Organometálicos/síntese química , Análise Espectral , Cristalografia por Raios X , Irídio/química , Modelos Moleculares , Oxirredução , Termodinâmica
11.
J Sep Sci ; 42(24): 3631-3639, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31651081

RESUMO

The interactive behavior of an amphipathic peptide with the Cu2+ , Ni2+ , and Zn2+ complexes of 1,4-bis(triazacyclonon-1-yl)butane), bis(tacn)but , immobilized onto Sepharose CL-4B, has been investigated. The effects of incubation time, as well as the incubation buffer pH and ionic strength, have been examined. The binding data have been interrogated using Langmuir, Langmuir-Freundlich, bi-Langmuir, and Temkin isothermal models and Scatchard plots. These results confirm that this amphipathic peptide binds with relatively high capacities to the immobilized Cu2+ - and Ni2+ -1,4-bis(triazacyclonon-1-yl)butane)-Sepharose CL-4B sorbents via at least two discrete sites. However, the corresponding immobilized Zn2+ -sorbent had low binding capacity. Moreover, the magnitude of the binding capacities of these sorbents was dependent on the pH and ionic strength of the incubation buffer. These results are relevant to the isolation of E. coli expressed recombinant proteins that incorporate this and related amphipathic peptide tags, containing two or more histidine residues, located at the N- or C-terminus of the recombinant protein, and the co-purification of low abundance host cell proteins of diverse structure, by immobilized metal ion affinity chromatographic methods.


Assuntos
Quelantes/química , Ciclobutanos/química , Compostos Organometálicos/química , Tensoativos/química , Zinco/química , Adsorção , Cromatografia de Afinidade , Ciclobutanos/síntese química , Histidina/química , Concentração de Íons de Hidrogênio , Ligantes , Metais Pesados/química , Compostos Organometálicos/síntese química , Peptídeos/química , Resinas Sintéticas/química , Cloreto de Sódio/química , Propriedades de Superfície
12.
Inorg Chem ; 58(21): 14720-14727, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31613605

RESUMO

Although alkaline earth metal cations play an important role in our daily life, little attention has been paid to the field of fast quantitative analysis of their content due to a lack of satisfactory precision and a fast and convenient means of detection. In this study, we have designed a set of molecular tweezers based on the calix[4]arene chemosensor L, which was found to exhibit high selectivity and sensitivity toward Ca2+, Sr2+, and Ba2+ (by UV-vis and fluorescence methods) with low detection limits of the order of 10-7 to 10-8 M and high association constants (of the order of 106). More significantly, sensor L not only can recognize Ca2+, Sr2+, and Ba2+ but also can further discriminate between these three cations via the differing red shifts in their UV-vis spectra (560 nm for L·Ca2+, 570 nm for L·Sr2+, and 580 nm for L·Ba2+ complex) which is attributed to their different atomic radii. A rare synergistic effect for the recognition mechanism has been demonstrated by 1H NMR spectroscopic titration. Sensor L constructed a high shielding field by the cooperation of Tris with alkaline earth metal ion after complex. Additionally, the presence of acetoxymethyl group in sensor L results in enhancement of cell permeability, and as a consequence, sensor L exhibited excellent sensing and imaging (in vivo) in living cells and in zebrafish.


Assuntos
Bário/análise , Cálcio/análise , Calixarenos/química , Metais Alcalinoterrosos/química , Imagem Óptica , Compostos Organometálicos/química , Fenóis/química , Estrôncio/análise , Animais , Sobrevivência Celular , Células HeLa , Humanos , Compostos Organometálicos/síntese química , Células Tumorais Cultivadas , Peixe-Zebra
13.
Eur J Med Chem ; 184: 111740, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31605864

RESUMO

The increasingly limited therapeutic options for the treatment of infections caused by multi-resistant Gram-negative bacteria due to the alarming increase in bacteria resistance, renewed interest in photodynamic inactivation (PDI) of bacteria. We address PDI of multi-resistant bacteria with a new family of cationic tetra-imidazolyl phthalocyanines bearing a diversity of cationizing alkylic chain sizes, degrees of cationization and coordinating metals. The antimicrobial activities of the phthalocyanines under white light against Gram-positive and Gram-negative bacteria have remarkable differences in efficacy. We relate their spectroscopic and photophysical properties with the generation of reactive oxygen species (ROS), biological performance and structural features. We show that sub-micromolar concentrations of a Zn(II) tetra-ethyl cationic phthalocyanine reduce colonies of Gram-negative bacteria (E. coli, P. aeruginosa) and C. albicans by 7 log units while leaving mammalian cells unharmed. This is a new lead to address hard-to-treat localized infections.


Assuntos
Antibacterianos/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Indóis/farmacologia , Compostos Organometálicos/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Indóis/química , Testes de Sensibilidade Microbiana , Microscopia Confocal , Estrutura Molecular , Imagem Óptica , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Processos Fotoquímicos , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Sais/síntese química , Sais/química , Sais/farmacologia , Relação Estrutura-Atividade
14.
Chem Biodivers ; 16(11): e1900322, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31544357

RESUMO

The synthesis of poly[N,N-bis(3-aminopropyl)glycine] (PAPGly) dendrons Gd-based contrast agents (GdCAs) via an orthogonal protection of the different functional groups and an activation/coupling strategy wherein a specific number of synthetic steps add a generation to the existing dendron has been described. The aim of this protocol is to build up two different generations of dendrons (G-0 or dendron's core, and G-1) with peripheral NH2 groups to conjugate a 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A) derivative and afterwards to chelate with Gd3+ paramagnetic ions. These complexes, which have a well-defined molecular weight, are of relevance to MRI as an attempt to gain higher 1 H relaxivity by slowing down the rotation of molecule compared to monomeric Gd(III) complexes used as contrast agents and to increase the number of paramagnetic centers present in one molecular structure. From the study of their water 1 H longitudinal relaxation rate at different magnetic fields (NMRD, Nuclear Magnetic Relaxation Dispersion) and by evaluating the variable temperature 17 O-NMR data we determined the parameters characterizing the water exchange rate and the rotational correlation time of each complex, both affecting 1 H relaxivity. Furthermore, these two novel PAPGly GdCAs were objects of i) an in vivo study to determine their biodistributions in healthy C57 mice at several time points, and ii) the Dynamic Contrast-Enhanced MRI (DCE-MRI) approach to assess their contrast efficiency measured in the tumor region of C57BL/6 mice transplanted subcutaneously with B16-F10 melanoma cells. The aim of the comparison of these two dendrons GdCAs, having different molecular weights (MW), is to understand how MW and relaxivity may influence the contrast enhancement capabilities in vivo at low magnetic field (1 T). Significant contrast enhancement was observed in several organs (vessel, spleen and liver), already at 5 min post-injection, for the investigated CAs. Moreover, these CAs induced a marked contrast enhancement in the tumor region, thanks to the enhanced permeability retention effect of those macromolecular structures.


Assuntos
Meios de Contraste/química , Gadolínio/química , Melanoma/química , Compostos Organometálicos/química , Animais , Meios de Contraste/síntese química , Meios de Contraste/farmacocinética , Gadolínio/farmacocinética , Humanos , Imagem por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Melanoma/diagnóstico por imagem , Camundongos , Camundongos Endogâmicos C57BL , Estrutura Molecular , Neoplasias Experimentais/química , Neoplasias Experimentais/diagnóstico por imagem , Compostos Organometálicos/síntese química , Compostos Organometálicos/farmacocinética , Distribuição Tecidual
15.
Eur J Med Chem ; 182: 111672, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31505452

RESUMO

Based on the unique role of a common unit in a family of sulfur-containing natural histone deacetylases (HDACs) inhibitors, we have chosen largazole as an example of these inhibitors and adopted a "fluorine scan" strategy towards modification of this common unit. Thus a set of fluoro largazole analogues has been designed, synthesized and evaluated in enzymatic as well as cellular assays. The preliminary results indicate that introduction of fluorine at the various position of the unit has an important impact on the activity and selectivity of HDACs. Unlike other modifications which often led to significant reduction or complete loss of activity as reported in the literature, most of these fluoro thiols have displayed comparable or enhanced activity and selectivity in enzymatic assays. Two of the sulfhydryl esters have also exhibited excellent inhibitory activity in cellular assays with a few selected cell lines. The C19-fluorinated analogue has been further studied by immunoblot analysis, confirming that it is a potent selective class I HDAC inhibitor and supporting that the potent cellular antiproliferative activity is due to HDAC inhibition. The molecular docking study reveals that introducing fluorine at the C19 position does not change the original interactions, but might have made a subtle change in binding conformation, resulting in an obvious improvement in activity.


Assuntos
Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/metabolismo , Compostos Organometálicos/farmacologia , Compostos de Sulfidrila/farmacologia , Zinco/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Inibidores de Histona Desacetilases/síntese química , Inibidores de Histona Desacetilases/química , Humanos , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Relação Estrutura-Atividade , Compostos de Sulfidrila/química , Zinco/química
16.
Chem Biodivers ; 16(11): e1900403, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31515947

RESUMO

The antibacterial and antibiofilm activities of two new ruthenium complexes against E. coli, S. aureus, P. aeruginosa PAO1 (laboratory strain) and P. aeruginosa LES B58 (clinical strain) were evaluated. Complexes, mer-[RuIII (2-bimc)3 ] ⋅ H2 O (1) and cis-[RuIV Cl2 (2,3-pydcH)2 ] ⋅ 4H2 O (2), were obtained using aromatic carboxylic acid ligands, namely, 1H-benzimidazole-2-carboxylic acid (2-bimcH) and pyridine-2,3-dicarboxylic acid (2,3-pydcH2 ). Compounds were physicochemically characterized using X-ray diffraction, Hirshfeld surface analysis, IR and UV/VIS spectroscopies, as well as magnetic and electrochemical measurements. Structural characterization revealed that Ru(III) and Ru(IV) ions in the complexes adopt a distorted octahedral geometry. The intermolecular classical and weak hydrogen bonds, and π⋅⋅⋅π contacts significantly contribute to structure stabilization, leading to the formation of a supramolecular assembly. Biological studies have shown that the Ru complexes inhibit the growth of bacteria and biofilm formation by the tested strains and the complexes seem to be a potential as antimicrobial agents.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Ácidos Carboxílicos/farmacologia , Compostos Organometálicos/farmacologia , Rutênio/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Ácidos Carboxílicos/química , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Pseudomonas aeruginosa/efeitos dos fármacos , Rutênio/química , Staphylococcus aureus/efeitos dos fármacos
17.
Int J Mol Sci ; 20(16)2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31430981

RESUMO

A library of isopulegol-based bi-, tri- and tetrafunctional chiral ligands has been developed from commercially available (-)-isopulegol and applied as chiral catalysts in the addition of diethylzinc to benzaldehyde. Michael addition of primary amines towards α-methylene-γ-butyrolactone, followed by reduction, was accomplished to provide aminodiols in highly stereoselective transformations. Stereoselective epoxidation of (+)-neoisopulegol, derived from natural (-)-isopulegol, and subsequent oxirane ring opening with primary amines afforded aminodiols. The regioselective ring closure of N-substituted aminodiols with formaldehyde was also investigated. Hydroxylation of (+)-neoisopulegol resulted in diol, which was then transformed into aminotriols by aminolysis of its epoxides. Dihydroxylation of (+)-neoisopulegol or derivatives with OsO4/NMO gave neoisopulegol-based di-, tri- and tetraols in highly stereoselective reactions. The antimicrobial activity of aminodiol and aminotriol derivatives as well as di-, tri- and tetraols was also explored. In addition, structure-activity relationships were examined by assessing substituent effects on the aminodiol and aminotriol systems.


Assuntos
Monoterpenos Cicloexânicos/síntese química , 4-Butirolactona/síntese química , 4-Butirolactona/química , Aminação , Amino Álcoois/síntese química , Amino Álcoois/química , Benzaldeídos/síntese química , Benzaldeídos/química , Catálise , Técnicas de Química Sintética , Monoterpenos Cicloexânicos/química , Ligantes , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Estereoisomerismo
18.
Inorg Chem ; 58(17): 11294-11299, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31411862

RESUMO

The first two examples of polyoxopalladates(II) (POPs) containing tetravalent metal ion guests, [MO8Pd12(PO4)8]12- (M = SnIV, PbIV), have been prepared and structurally characterized in the solid state, solution, and gas phase. The interactions of the metal ion guests and the palladium-oxo shell were studied by theoretical calculations. The POPs were shown to possess anticancer activity by causing oxidative stress inducing caspase activation and consecutive apoptosis of leukemic cells.


Assuntos
Antineoplásicos/farmacologia , Metais Pesados/química , Compostos Organometálicos/farmacologia , Polímeros/química , Antineoplásicos/síntese química , Antineoplásicos/química , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Células HL-60 , Humanos , Íons/química , Modelos Moleculares , Compostos Organometálicos/síntese química , Compostos Organometálicos/química
19.
Biol Trace Elem Res ; 192(2): 153-159, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31407215

RESUMO

Metal complexes for medical applications are the promising area of research and metallo-drugs have been developed and evaluated to enhance the efficiency of drugs and minimize their side effects. This study describes the synthesis of a Schiff base ligand (Z)-3-bromo-5-((p-tolylimino)methyl)phenol from the reaction of 5-bromosalicilaldehyde and p-toluidine, and its subsequent complexation with nickel. Characterization and cell viability studies were performed for both Schiff base ligand and its metal complex with 1H-NMR, FTIR, TG analysis, and UV-VIS spectrometry. With the aim of proving the Ni complex formation, quantitative analysis was done with flame atomic absorption spectrometry. The recovery result obtained for the formed complex was 103.9%. The cell viability of human thyroid gland undifferentiated carcinoma cells (8305C) treated with the Ni-ligand complex was determined as 12.7 ± 0.17%. It was observed that the nickel complex could be a significant anticancer agent as tested by the MTT assay method. Graphical Abstract .


Assuntos
Antineoplásicos/farmacologia , Níquel/farmacologia , Compostos Organometálicos/farmacologia , Neoplasias da Glândula Tireoide/tratamento farmacológico , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Ligantes , Camundongos , Níquel/química , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Bases de Schiff/química , Bases de Schiff/farmacologia , Neoplasias da Glândula Tireoide/patologia
20.
Photochem Photobiol Sci ; 18(8): 2012-2022, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31282525

RESUMO

Organic-metal complexes are promising molecules for use in photodynamic therapy (PDT). The aim of this study was to investigate in vitro effects of novel Ru(ii) and Ir(iii) BODIPY complexes for PDT. These hybrid organic-metal molecules (Ru-BD and Ir-BD) have been synthesized via reactions of a BODIPY precursor (BD) with a phenanthroline unit bearing Ru(ii) (3) and novel Ir(iii) (4) compounds. The crystal structures of the new distyryl BODIPY (BD) and Ru(ii) complex (3) are also reported. The photophysical and singlet oxygen generation properties of Ru-BD and Ir-BD were investigated in comparison with unsubstituted BODIPY (BD). Moreover, Ru-BD and Ir-BD have been biologically evaluated in vitro in chronic myeloid leukemia and cervical cancer cell lines in terms of photodynamic therapy efficacy in the presence of BD control. These complexes were not toxic in the dark but red light was needed to induce cell death. These data support the fact that Ru-BD could be accepted as a valuable photosensitizer-drug for further PDT treatment.


Assuntos
Antineoplásicos/farmacologia , Compostos de Boro/farmacologia , Corantes/farmacologia , Compostos Organometálicos/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Boro/síntese química , Compostos de Boro/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Corantes/síntese química , Corantes/química , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Irídio/química , Irídio/farmacologia , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Rutênio/química , Rutênio/farmacologia , Oxigênio Singlete/análise , Oxigênio Singlete/metabolismo , Células Tumorais Cultivadas
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