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1.
Int J Mol Sci ; 22(6)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803618

RESUMO

A series of thiosemicarbazone derivatives was prepared and their anti-tumor activity in vitro was tested. The X-ray investigation performed for compounds T2, T3 and T5 confirmed the synthesis pathway and assumed molecular structures of analyzed thiosemicarbazones. The conformational preferences of the thiosemicarbazone system were characterized using theoretical calculations by AM1 method. Selected compounds were converted into complexes of Cu (II) ions. The effect of complexing on anti-tumor activity has been investigated. The copper(II) complexes, with Schiff bases T1, T10, T12, T13, and T16 have been synthesized and characterized by chemical and elemental analysis, FTIR spectroscopy and TGA method. Thermal properties of coordination compounds were studied using TG-DTG techniques under dry air atmosphere. G361, A375, and SK-MEL-28 human melanoma cells and BJ human normal fibroblast cells were treated with tested compounds and their cytotoxicity was evaluated with MTT test. The compounds with the most promising anti-tumour activity were then selected and their cytotoxicity was verified with cell cycle analysis and apoptosis/necrosis detection. Additionally, DNA damages in the form of a basic sites presence and the expression of oxidative stress and DNA damage response genes were evaluated. The obtained results indicate that complexation of thiosemicarbazone derivatives with Cu (II) ions improves their antitumor activity against melanoma cells. The observed cytotoxic effect is associated with DNA damage and G2/M phase of cell cycle arrest as well as disorders of the antioxidant enzymes expression.


Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Cobre/farmacologia , Melanoma/patologia , Tiossemicarbazonas/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/química , Cobre/química , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Ligação de Hidrogênio , Concentração Inibidora 50 , Íons , Melanoma/genética , Conformação Molecular , Necrose , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Temperatura , Tiossemicarbazonas/química
2.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 52(2): 241-247, 2021 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-33829698

RESUMO

Objective: To synthesize three kinds of metal complexes of aloe-emodin and compare the antioxidant activities of the ligands and the complexes. Methods: Three kinds of aloe emodin metal complex, the aloe-emodin-iron (Ⅱ), the aloe-emodin-copper (Ⅱ) and the aloe-emodin-magnesium (Ⅱ) complexes, were synthesized by dissolving and stirring in anhydrous ethanol solvent, and their structures were characterized. The Fe 2+-H 2O 2-methylene blue method, the diphenyl bitter hydrazine radical method (DPPH method) and other assays were used to determine the clearance effect of ligands and complexes on superoxide radicals (O 2 -•), hydroxyl radicals (•OH) and phenyl bitter hydrazine radical (DPPH•). Results: Three kinds of aloe emodin metal complex, the aloe-emodin-iron (Ⅱ), the aloe-emodin-copper (Ⅱ) and the aloe-emodin-magnesium (Ⅱ) complexes, were successfully synthesized. According to the results of structural characterization, we speculated that the aloe-emodin metal complexes were formed at the site between the two molecules of aloe-emodin and one molecule of metal ions (Fe 2+, Mg 2+, Cu 2+) via the 9 th carbonyl and 8 th hydroxyl groups of the aloe-emodin molecules. Both the complex and the ligand have clearance effects on three kinds of free radicals, and the complex showed stronger effects than its ligand ( P<0.05). Conclusion: Coordination of aloe-emodin with metal ions, such as Fe 2+, Cu 2+, and Mg 2+, could enhance the antioxidant activity of the ligand itself.


Assuntos
Aloe , Complexos de Coordenação , Emodina , Antraquinonas , Antioxidantes
3.
PLoS One ; 16(3): e0246265, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33661932

RESUMO

Medicinal uses and applications of metals and their complexes are of increasing clinical and commercial importance. The ligation behavior of quercetin (Q), which is a flavonoid, and its Zn (II) (Q/Zn) complex were studied and characterized based on elemental analysis, molar conductance, Fourier-transform infrared (FTIR) spectra, electronic spectra, proton nuclear magnetic resonance (1H-NMR), thermogravimetric analysis, and transmission electron microscopy (TEM). FTIR spectral data revealed that Q acts as a bidentate ligand (chelating ligand) through carbonyl C(4) = O oxygen and phenolic C(3)-OH oxygen in conjugation with Zn. Electronic, FTIR, and 1H-NMR spectral data revealed that the Q/Zn complex has a distorted octahedral geometry, with the following chemical formula: [Zn(Q)(NO3)(H2O)2].5H2O. Diabetes was induced by streptozotocin (STZ) injection. A total of 70 male albino rats were divided into seven groups: control, diabetic untreated group and diabetic groups treated with either MSCs and/or Q and/or Q/Zn or their combination. Serum insulin, glucose, C-peptide, glycosylated hemoglobin, lipid profile, and enzymatic and non-enzymatic antioxidant levels were determined. Pancreatic and lung histology and TEM for pancreatic tissues in addition to gene expression of both SOD and CAT in pulmonary tissues were evaluated. MSCs in combination with Q/Zn therapy exhibited potent protective effects against STZ induced hyperglycemia and suppressed oxidative stress, genotoxicity, glycometabolic disturbances, and structural alterations. Engrafted MSCs were found inside pancreatic tissue at the end of the experiment. In conclusion, Q/Zn with MSC therapy produced a synergistic effect against oxidative stress and genotoxicity and can be considered potential ameliorative therapy against diabetes with pulmonary dysfunction, which may benefit against COVID-19.


Assuntos
Diabetes Mellitus Experimental/terapia , Hipoglicemiantes/uso terapêutico , Transplante de Células-Tronco Mesenquimais , Quercetina/uso terapêutico , Zinco/uso terapêutico , Animais , Glicemia/análise , Glicemia/metabolismo , Peptídeo C/sangue , Peptídeo C/metabolismo , Células Cultivadas , Complexos de Coordenação/química , Complexos de Coordenação/uso terapêutico , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Hemoglobina A Glicada/análise , Hemoglobina A Glicada/metabolismo , Hiperglicemia/sangue , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Hiperglicemia/terapia , Hipoglicemiantes/química , Insulina/sangue , Insulina/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Estresse Oxidativo/efeitos dos fármacos , Quercetina/análogos & derivados , Ratos , Zinco/química
4.
Int J Mol Sci ; 22(4)2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33670389

RESUMO

The present article demonstrates selective cytotoxicity against cancer cells of the complexes [Co(LD)2]I2∙CH3OH (1), [CoLD(NCS)2] (2) and [VOLD(NCS)2]∙C6H5CH3 (3) containing the dipodal tridentate ligand LD = N,N-bis(3,5-dimethylpyrazol-1-ylmethyl)amine), formed in situ. All tested complexes expressed greater anticancer activities and were less toxic towards noncancerous cells than cisplatin. Cobalt complexes (1 and 2) combined high cytotoxicity with selectivity towards cancer cells and caused massive tumour cell death. The vanadium complex (3) induced apoptosis specifically in cancer cells and targeted proteins, controlling their invasive and metastatic properties. The presented experimental data and computational prediction of drug ability of coordination compounds may be helpful for designing novel and less toxic metal-based anticancer species with high specificities towards tumour cells.


Assuntos
Antineoplásicos , Complexos de Coordenação , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Células CHO , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cricetulus , Células Hep G2 , Humanos , Ligantes , Neoplasias/metabolismo , Neoplasias/patologia
5.
Carbohydr Polym ; 261: 117821, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33766331

RESUMO

Damage to the cell membrane is an effective method to prevent drug resistance in plant fungal diseases. Here, we proposed a negative remodeling model of the cell membrane structure induced by the C-coordinated O-carboxymethyl chitosan Cu (II) complex (O-CSLn-Cu). FITC-labeled O-CSLn-Cu (FITC-O-CSLn-Cu) was first synthesized via a nucleophilic substitution reaction and confirmed by FT-IR. FITC-labeled O-CSLn-Cu could pass through the fungal cell membrane, as detected by confocal laser scanning microscopy (CLSM) coupled with fluorescein isothiocyanate (FITC)-fluorescence. O-CSLn-Cu treatment led to apparent morphological changes in the membranes of P. capsici Leonian and giant unilamellar vesicles (GUVs) by transmission electron microscopy (TEM). Then, we performed component analysis of the cell membrane from the P. capsici Leonian affected by O-CSLn-Cu with a particular interest in membrane physicochemical properties. Many unsaturated fatty acids (UFAs) and key enzymes promoting UFA synthesis of the cell membrane were downregulated. Similarly, a large number of membrane proteins responsible for substance transport and biochemical reactions were downregulated. Furthermore, O-CSLn-Cu treatments increased plasma membrane permeability with significant leakage of intercellular electrolytes, soluble proteins and sugars, and lipid peroxidation with decreasing membrane fluidity. Finally, aquaporin 10 was proven to be a potential molecular target sensitive to antimicrobial agents according to composition analysis of membrane structure and immunohistochemistry.


Assuntos
Antifúngicos/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Quitosana/análogos & derivados , Cobre/química , Phytophthora/efeitos dos fármacos , Animais , Antifúngicos/síntese química , Antifúngicos/química , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Quitosana/química , Quitosana/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Cobre/farmacologia , Fungicidas Industriais/síntese química , Fungicidas Industriais/química , Fungicidas Industriais/farmacologia , Fluidez de Membrana/efeitos dos fármacos , Lipídeos de Membrana/fisiologia , Phytophthora/metabolismo , Phytophthora/ultraestrutura , Coelhos , Esporos/efeitos dos fármacos , Esporos/fisiologia
6.
Molecules ; 26(4)2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33671247

RESUMO

In the present study, naphthyl acetohydrazide (HL) ligand was prepared and used for the synthesis of new six amorphous transition metal (Co(II), Ni(II), Cu(II), Zn(II), Pb(II), Cd(II)) complexes. All the compounds were characterized by elemental analysis, UV-vis, FT-IR, 1H- and 13C-NMR, and Matrix-Assisted Laser Desorption Ionization (MALDI). The solubilization study was carried out by estimating the interaction between the metal complexes with surfactants viz. sodium stearate (SS) and Cetyltrimethylammonium bromide (CTAB). UV-Visible spectroscopy was employed to determine partitioning and binding parameters, whereas electrical conductivity measurements were employed to estimate critical micellar concentration (CMC), the extent of dissociation, and free energy of micellization. The CT-DNA interaction of synthesized compounds with DNA represents the major groove binding. The synthesized ligand and metal complexes were also tested against bacterial and fungal strains and it has been observed that Cu(II) complex is active against all the strains except Candida albicans, while Cd(II) complex is active against all bacterial and fungal strains except Pseudomonas. Among all compounds, only the Pd(II) complex shows reasonable activity against cervical cancer HeLa cell lines, representing 97% inhibition.


Assuntos
Anti-Infecciosos/farmacologia , Complexos de Coordenação/síntese química , DNA/metabolismo , Hidrazonas/síntese química , Hidrazonas/farmacologia , Metais/química , Micelas , Neoplasias/patologia , Bactérias/efeitos dos fármacos , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Sobrevivência Celular/efeitos dos fármacos , Condutividade Elétrica , Células HeLa , Humanos , Hidrazonas/química , Ligantes , Testes de Sensibilidade Microbiana , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Tensoativos/química
7.
Molecules ; 26(4)2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33671758

RESUMO

As a candidate for bifunctional asymmetric catalysts containing a half-sandwich C-N chelating Ir(III) framework (azairidacycle), a dinuclear Ir complex with an axially chiral linkage is newly designed. An expedient synthesis of chiral 2,2'-bis(aminomethyl)-1,1'-binaphthyl (1) from 1,1-bi-2-naphthol (BINOL) was accomplished by a three-step process involving nickel-catalyzed cyanation and subsequent reduction with Raney-Ni and KBH4. The reaction of (S)-1 with an equimolar amount of [IrCl2Cp*]2 (Cp* = η5-C5(CH3)5) in the presence of sodium acetate in acetonitrile at 80 °C gave a diastereomeric mixture of new dinuclear dichloridodiiridium complexes (5) through the double C-H bond cleavage, as confirmed by 1H NMR spectroscopy. A loss of the central chirality on the Ir centers of 5 was demonstrated by treatment with KOC(CH3)3 to generate the corresponding 16e amidoiridium complex 6. The following hydrogen transfer from 2-propanol to 6 provided diastereomers of hydrido(amine)iridium retaining the bis(azairidacycle) architecture. The dinuclear chlorido(amine)iridium 5 can serve as a catalyst precursor for the asymmetric transfer hydrogenation of acetophenone with a substrate to a catalyst ratio of 200 in the presence of KOC(CH3)3 in 2-propanol, leading to (S)-1-phenylethanol with up to an enantiomeric excess (ee) of 67%.


Assuntos
Compostos Aza/química , Complexos de Coordenação/química , Irídio/química , Naftalenos/química , Complexos de Coordenação/síntese química , Conformação Molecular
8.
Molecules ; 26(4)2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33671782

RESUMO

CrCl3(thf)3 is a common starting material in the synthesis of organometallic and coordination compounds of Cr. Deposited as an irregular solid with no possibility of recrystallization, it is not a purity guaranteed chemical, causing problems in some cases. In this work, we disclose a well-defined form of the THF adduct of CrCl3 ([CrCl2(µ-Cl)(thf)2]2), a crystalline solid, that enables structure determination by X-ray crystallography. The EA data and XRD pattern of the bulk agreed with the revealed structure. Moreover, its preparation procedure is facile: evacuation of CrCl3·6H2O at 100 °C, treatment with 6 equivalents of Me3SiCl in a minimal amount of THF, and crystallization from CH2Cl2. The ethylene tetramerization catalyst [iPrN{P(C6H4-p-Si(nBu)3)2}2CrCl2]+[B(C6F5)4]- prepared using well-defined [CrCl2(µ-Cl)(thf)2]2 as a starting material exhibited a reliably high activity (6600 kg/g-Cr/h; 1-octene selectivity at 40 °C, 75%), while that of the one prepared using the impure CrCl3(thf)3 was inconsistent and relatively low (~3000 kg/g-Cr/h). By using well-defined [CrCl2(µ-Cl)(thf)2]2 as a Cr source, single crystals of [(CH3CN)4CrCl2]+[B(C6F5)4]- and [{Et(Cl)Al(N(iPr)2)2}Cr(µ-Cl)]2 were obtained, allowing structure determination by X-ray crystallography, which had been unsuccessful when the previously known CrCl3(thf)3 was used as the Cr source.


Assuntos
Cromo/química , Complexos de Coordenação/química , Furanos/química , Complexos de Coordenação/síntese química , Cristalografia por Raios X , Modelos Moleculares , Estrutura Molecular
9.
Molecules ; 26(4)2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33672166

RESUMO

The search for two- and three-dimensional materials with slow relaxation of the magnetization (single-ion magnets, SIM and single-molecule magnets, SMM) has become a very active area in recent years. Here we show how it is possible to prepare two-dimensional SIMs by combining Dy(III) with two different anilato-type ligands (dianions of the 3,6-disubstituted-2,5-dihydroxy-1,4-benzoquinone: C6O4X22-, with X = H and Cl) in dimethyl sulfoxide (dmso). The two compounds prepared, formulated as: [Dy2(C6O4H2)3(dmso)2(H2O)2]·2dmso·18H2O (1) and [Dy2(C6O4Cl2)3(dmso)4]·2dmso·2H2O (2) show distorted hexagonal honeycomb layers with the solvent molecules (dmso and H2O) located in the interlayer space and in the hexagonal channels that run perpendicular to the layers. The magnetic measurements of compounds 1, 2 and [Dy2(C6O4(CN)Cl)3(dmso)6] (3), a recently reported related compound, show that the three compounds present slow relaxation of the magnetization. In compound 1 the SIM behaviour does not need the application of a DC field whereas 2 and 3 are field-induced SIM (FI-SIM) since they show slow relaxation of the magnetization when a DC field is applied. We discuss the differences observed in the crystal structures and magnetic properties based on the X group of the anilato ligands (H, Cl and Cl/CN) in 1-3 and in the recently reported derivative [Dy2(C6O4Br2)3(dmso)4]·2dmso·2H2O (4) with X = Br, that is also a FI-SIM.


Assuntos
Benzoquinonas/química , Complexos de Coordenação/química , Disprósio/química , Modelos Moleculares , Estrutura Molecular
10.
Molecules ; 26(4)2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672662

RESUMO

A new series of tetrahedral heteroleptic copper(I) complexes exhibiting efficient thermally-activated delayed fluorescence (TADF) in green to orange electromagnetic spectral regions has been developed by using D-A type N^N ligand and P^P ligands. Their structures, electrochemical, photophysical, and electroluminescence properties have been characterized. The complexes exhibit high photoluminescence quantum yields (PLQYs) of up to 0.71 at room temperature in doped film and the lifetimes are in a wide range of 4.3-24.1 µs. Density functional theory (DFT) calculations on the complexes reveal the lowest-lying intraligand charge-transfer excited states that are localized on the N^N ligands. Solution-processed organic light emitting diodes (OLEDs) based on one of the new emitters show a maximum external quantum efficiency (EQE) of 7.96%.


Assuntos
Complexos de Coordenação/química , Cobre/química , Corantes Fluorescentes/química , Teoria Quântica , Temperatura , Ligantes , Estrutura Molecular , Soluções
11.
Molecules ; 26(4)2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672781

RESUMO

(1) Background: Exopolysaccharide (EPS) derivatives, produced by Alteromonas infernus bacterium, showed anti-metastatic properties. They may represent a new class of ligands to be combined with theranostic radionuclides, such as 47Sc/44Sc. The goal of this work was to investigate the feasibility of such coupling. (2) Methods: EPSs, as well as heparin used as a drug reference, were characterized in terms of molar mass and dispersity using Asymmetrical Flow Field-Flow Fractionation coupled to Multi-Angle Light Scattering (AF4-MALS). The intrinsic viscosity of EPSs at different ionic strengths were measured in order to establish the conformation. To determine the stability constants of Sc with EPS and heparin, a Free-ion selective radiotracer extraction (FISRE) method has been used. (3) Results: AF4-MALS showed that radical depolymerization produces monodisperse EPSs, suitable for therapeutic use. EPS conformation exhibited a lower hydrodynamic volume for the highest ionic strengths. The resulting random-coiled conformation could affect the complexation with metal for high concentration. The LogK of Sc-EPS complexes have been determined and showing that they are comparable to the Sc-Hep. (4) Conclusions: EPSs are very promising to be coupled with the theranostic pair of scandium for Nuclear Medicine.


Assuntos
Alteromonas/química , Complexos de Coordenação/química , Polissacarídeos/química , Escândio/química , Configuração de Carboidratos , Fracionamento por Campo e Fluxo , Hidrodinâmica , Luz , Medicina Nuclear , Concentração Osmolar , Espalhamento de Radiação , Nanomedicina Teranóstica , Viscosidade
12.
Molecules ; 26(4)2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33672016

RESUMO

Reaction of 2,2'-bipyridine (2,2'-bipy) or 1,10-phenantroline (phen) with [Mn(Piv)2(EtOH)]n led to the formation of binuclear complexes [Mn2(Piv)4L2] (L = 2,2'-bipy (1), phen (2); Piv- is the anion of pivalic acid). Oxidation of 1 or 2 by air oxygen resulted in the formation of tetranuclear MnII/III complexes [Mn4O2(Piv)6L2] (L = 2,2'-bipy (3), phen (4)). The hexanuclear complex [Mn6(OH)2(Piv)10(pym)4] (5) was formed in the reaction of [Mn(Piv)2(EtOH)]n with pyrimidine (pym), while oxidation of 5 produced the coordination polymer [Mn6O2(Piv)10(pym)2]n (6). Use of pyrazine (pz) instead of pyrimidine led to the 2D-coordination polymer [Mn4(OH)(Piv)7(µ2-pz)2]n (7). Interaction of [Mn(Piv)2(EtOH)]n with FeCl3 resulted in the formation of the hexanuclear complex [MnII4FeIII2O2(Piv)10(MeCN)2(HPiv)2] (8). The reactions of [MnFe2O(OAc)6(H2O)3] with 4,4'-bipyridine (4,4'-bipy) or trans-1,2-(4-pyridyl)ethylene (bpe) led to the formation of 1D-polymers [MnFe2O(OAc)6L2]n·2nDMF, where L = 4,4'-bipy (9·2DMF), bpe (10·2DMF) and [MnFe2O(OAc)6(bpe)(DMF)]n·3.5nDMF (11·3.5DMF). All complexes were characterized by single-crystal X-ray diffraction. Desolvation of 11·3.5DMF led to a collapse of the porous crystal lattice that was confirmed by PXRD and N2 sorption measurements, while alcohol adsorption led to porous structure restoration. Weak antiferromagnetic exchange was found in the case of binuclear MnII complexes (JMn-Mn = -1.03 cm-1 for 1 and 2). According to magnetic data analysis (JMn-Mn = -(2.69 ÷ 0.42) cm-1) and DFT calculations (JMn-Mn = -(6.9 ÷ 0.9) cm-1) weak antiferromagnetic coupling between MnII ions also occurred in the tetranuclear {Mn4(OH)(Piv)7} unit of the 2D polymer 7. In contrast, strong antiferromagnetic coupling was found in oxo-bridged trinuclear fragment {MnFe2O(OAc)6} in 11·3.5DMF (JFe-Fe = -57.8 cm-1, JFe-Mn = -20.12 cm-1).


Assuntos
Acetatos/química , Complexos de Coordenação/química , Compostos Heterocíclicos/química , Manganês/química , Valeratos/química , Adsorção , Complexos de Coordenação/síntese química , Cristalografia por Raios X , Espectroscopia de Ressonância de Spin Eletrônica , Fenômenos Magnéticos , Conformação Molecular , Temperatura , Termogravimetria , Valeratos/síntese química , Difração de Raios X
13.
Molecules ; 26(5)2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673411

RESUMO

This study investigates the coordination chemistry of the tetradentate pyridine-containing 12-membered macrocycles L1-L3 towards Platinum Group metal ions PdII, PtII, and RhIII. The reactions between the chloride salts of these metal ions and the three ligands in MeCN/H2O or MeOH/H2O (1:1 v/v) are shown, and the isolated solid compounds are characterized, where possible, by mass spectroscopy and 1H- and 13C-NMR spectroscopic measurements. Structural characterization of the 1:1 metal-to-ligand complexes [Pd(L1)Cl]2[Pd2Cl6], [Pt(L1)Cl](BF4), [Rh(L1)Cl2](PF6), and [Rh(L3)Cl2](BF4)·MeCN shows the coordinated macrocyclic ligands adopting a folded conformation, and occupying four coordination sites of a distorted square-based pyramidal and octahedral coordination environment for the PdII/PtII, and RhIII complexes, respectively. The remaining coordination site(s) are occupied by chlorido ligands. The reaction of L3 with PtCl2 in MeCN/H2O gave by serendipity the complex [Pt(L3)(m-1,3-MeCONH)PtCl(MeCN)](BF4)2·H2O, in which two metal centers are bridged by an amidate ligand at a Pt1-Pt2 distance of 2.5798(3) Å and feature one square-planar and one octahedral coordination environment. Density Functional Theory (DFT) calculations, which utilize the broken symmetry approach (DFT-BS), indicate a singlet d8-d8 PtII-PtII ground-state nature for this compound, rather than the alleged d9-d7 PtI-PtIII mixed-valence character reported for related dinuclear Pt-complexes.


Assuntos
Complexos de Coordenação/química , Compostos Macrocíclicos/química , Paládio/química , Platina/química , Piridinas/química , Ródio/química , Cristalografia por Raios X , Teoria da Densidade Funcional , Ligantes , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Modelos Moleculares , Estrutura Molecular
14.
Eur J Med Chem ; 216: 113262, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33711764

RESUMO

The number of cancer cases continues to increase worldwide, and unfortunately the main systemic treatments available have numerous of side effects. Ruthenium complexes have shown to be promising chemotherapeutic agents, since they present low toxicity and are more selective for tumor tissues. We report the synthesis, characterization and biological properties of two new ruthenium (II) complexes containing Lapachol and Lawsone as ligands: (1) [Ru(Law)(dppb)(phen)]PF6 and (2) [Ru(Lap)(dppb)(phen)]PF6, where Law = Lawsone, Lap = Lapachol, dppb = 1,4-bis(diphenylphosphine)butane and phen = 1,10-phenanthroline. The ability of the complexes (1) and (2) to interact with CT-DNA (Calf Thymus) was investigated, and the results indicate that the complexes have shown a weak interaction with this macromolecule. Complexes (1) and (2) showed a moderate interaction with BSA, via a spontaneous process with the involvement of van der Waals and hydrogen bond interactions. Both complexes were tested against human lung cancer cell lines, chronic human myeloid leukemia, murine melanoma and human cervical and non-tumoral murine fibroblast adenocarcinoma, human lung fibroblasts and monkey kidney epithelia. The potential for cytotoxicity was tested out using the MTT assay and the neutral red test, to calculate inhibitory concentrations (IC50) and selectivity indices (IS). Both complexes showed a higher selectivity index of 1.17 and 10.91, respectively, for the HeLa tumor line. Studies of toxicological evaluation, using the micronucleus test and the comet assay against non-tumor cells, as well as an assessment of the potential for acute toxicity and neurotoxicity in zebrafish (Danio rerio). In the in vitro micronucleus test, complex (1) showed the least genotoxic potential, and in the in vitro comet assay both compounds had revealed a genotoxic potential at 0.5 and 1.0 mg L-1, with no difference between 24 h and 48 h exposure times. In the acute toxicity tests on zebrafish embryos, complex (1) showed sublethal effects such as decreased blood circulation and heartbeat rate, which were less pronounced than with complex (2). In contrast to complex 2, which caused lethality even before 48h, complex (1) did not cause the death of the embryos at concentrations up to (2.0 mg L-1). Complex (2) also lead to a delay in the embryo. Cell based in vitro methods thus proved able to provide specific toxicological data, allowing a significant reduction in ∖animal experimentation. Given that in vitro tests cannot completely replace animal tests, the use of less advanced developmental stages such as zebrafish embryos, which - at least in the European Union - are not regarded protected, could be shown to be an excellent alternative for testing with, e.g., mammals.


Assuntos
Complexos de Coordenação/química , Rutênio/química , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/metabolismo , Complexos de Coordenação/farmacologia , Cristalografia por Raios X , DNA/química , DNA/metabolismo , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Humanos , Conformação Molecular , Ligação Proteica , Soroalbumina Bovina/química , Soroalbumina Bovina/metabolismo , Termodinâmica , Peixe-Zebra/crescimento & desenvolvimento
15.
Eur J Med Chem ; 216: 113308, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33713976

RESUMO

Unique structure, characteristic reactivity, and facile synthesis of metal complexes have made them efficient ligands in drug development research. Among them, rhodium complexes have a limited history and there are a few discussions about their biological activities documented in the literature. However, investigation of kinetically inert rhodium complexes has recently attracted lots of attention and especially there are various evidences on their anti-cancer activity. It seems that they can be investigated as a versatile surrogates or candidates for the existing drugs which do not affect selectively or suffer from various side effects. In recent years, there has been an increasing interest in the use of mononuclear rhodium (III) organometallo drugs due to its versatile structurally important aspects to inhibit various enzymes. It has been demonstrated that organometallic Rh complexes profiting from both organic and inorganic aspects have shown more potent biological activities than classical inorganic compartments. In this respect, smart design, use of the appropriate organic ligands, and efficient and user-friendly synthesis of organometallic Rh complexes have played crucial roles in the inducing desirable biological activities. In this review, we focused on the recent advances published on the bioactivity of Rh (III/II/I) complexes especially inhibitory activity, from 2013 till now. Accordingly, considering the structure-activity relationship (SAR), the effect of oxidation state (+1, +2, and +3) and geometry (dimer or monomer complexes with coordination number of 4 and 6) of Rh complexes as well as various ligands on in vitro and in vivo studies was comprehensively discussed.


Assuntos
Complexos de Coordenação/química , Descoberta de Drogas , Ródio/química , Complexos de Coordenação/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Humanos , Isomerases/antagonistas & inibidores , Isomerases/metabolismo , Oxirredutases/antagonistas & inibidores , Oxirredutases/metabolismo , Proteínas Quinases/química , Proteínas Quinases/metabolismo , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismo , Relação Estrutura-Atividade
16.
Molecules ; 26(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652775

RESUMO

Europium (III) luminescent chelates possess intrinsic photophysical properties that are extremely useful in a wide range of applications. The lack of examples of coumarin-based lanthanide complexes is mainly due to poor photo-sensitization attempts. However, with the appeal of using such a versatile scaffold as antenna, especially in the development of responsive molecular probes, it is worth the effort to research new structural motifs. In this work, we present a series of two new tris coumarin-dipicolinate europium (III) complexes, specifically tailored to be either a mono or a dual emitter, tuning their properties with a simple chemical modification. We also encountered a rich chemical speciation in solution, studied in detail by means of paramagnetic NMR and emission spectroscopy.


Assuntos
Complexos de Coordenação/química , Cumarínicos/química , Európio/química , Sondas Moleculares/química , Quelantes/química , Elementos da Série dos Lantanídeos/química , Luminescência , Espectroscopia de Ressonância Magnética
17.
Molecules ; 26(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652788

RESUMO

Molybdates are biocidal materials that can be useful in coating surfaces that are susceptible to contamination and the spread of microorganisms. The aim of this work was to investigate the effects of copper doping of hydrated cobalt molybdate, synthesized by the co-precipitation method, on its antibacterial activity and to elucidate the structural and morphological changes caused by the dopant in the material. The synthesized materials were characterized by PXRD, Fourier Transformed Infrared (FTIR), thermogravimetric analysis/differential scanning calorimetry (TG/DSC), and SEM-Energy Dispersive Spectroscopy (SEM-EDS). The antibacterial response of the materials was verified using the Minimum Inhibitory Concentration (MIC) employing the broth microdilution method. The size of the CoMoO4·1.03H2O microparticles gradually increased as the percentage of copper increased, decreasing the energy that is needed to promote the transition from the hydrated to the beta phase and changing the color of material. CoMoO4·1.03H2O obtained better bactericidal performance against the tested strains of Staphylococcus aureus (gram-positive) than Escherichia coli (gram-negative). However, an interesting point was that the use of copper as a doping agent for hydrated cobalt molybdate caused an increase of MIC value in the presence of E. coli and S. aureus strains. The study demonstrates the need for caution in the use of copper as a doping material in biocidal matrices, such as cobalt molybdate.


Assuntos
Anti-Infecciosos/química , Cobalto/química , Cobre/química , Molibdênio/química , Anti-Infecciosos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Complexos de Coordenação/química , Escherichia coli/efeitos dos fármacos , Humanos , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Staphylococcus aureus/efeitos dos fármacos
18.
Molecules ; 26(5)2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33673610

RESUMO

Generally, bacteriochlorophyllides were responsible for the photosynthesis in bacteria. Seven types of bacteriochlorophyllides have been disclosed. Bacteriochlorophyllides a/b/g could be synthesized from divinyl chlorophyllide a. The other bacteriochlorophyllides c/d/e/f could be synthesized from chlorophyllide a. The chemical structure and synthetic route of bacteriochlorophyllides were summarized in this review. Furthermore, the potential applications of bacteriochlorophyllides in photosensitizers, immunosensors, influence on bacteriochlorophyll aggregation, dye-sensitized solar cell, heme synthesis and for light energy harvesting simulation were discussed.


Assuntos
Bactérias/metabolismo , Clorofilídios/biossíntese , Clorofilídios/química , Complexos de Coordenação/química , Técnicas Biossensoriais , Vias Biossintéticas , Heme/química , Heme/metabolismo , Fármacos Fotossensibilizantes/química , Fotossíntese , Energia Solar
19.
Molecules ; 26(5)2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33670937

RESUMO

The new symmetric acyclic N,N'-bis(1-pyrenyl) squaramide (H2L) functionalized with the pyrene moiety as a fluorogenic fragment has been designed and its ability to selectively detect specific anions and metals investigated. H2L selectively binds Cl- both in solution (DMSO 0.5% H2O and MeCN) and in the solid state, and allows to selectively detect Cu2+ in MeCN with the formation of a 2:1 metal-receptor complex, with a green intense emission appreciable by naked eye under the UV lamp. The H2L copper complex preserves its emission properties in the presence of Cl-. The addition of basic anions (OH-, CN-, and F-) up to 10 equivalents caused the deprotonation of the squaramide NHs and a dramatic change of the emission properties of the H2L copper complex.


Assuntos
Complexos de Coordenação/química , Cobre/química , Pirenos/química , Quinina/análogos & derivados , Acetonitrilos/química , Ânions/química , Teoria da Densidade Funcional , Modelos Moleculares , Conformação Molecular , Quinina/química , Espectrometria de Fluorescência
20.
Clin Nucl Med ; 46(5): 389-395, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33782298

RESUMO

PURPOSE: This pilot study tested the principle that 177Lu-DOTATATE may be applied to patients with high-grade gliomas (HGGs) that are either inoperable or refractory to the standard conventional treatments and also assessed whether this approach could be a viable therapeutic plan in this dilemma. METHODS: In this prospective study, 16 subjects experiencing HGGs that were either inoperable or refractory to the standard conventional treatments were included. All the patients checked for somatostatin receptor expression on the tumors. The patients were treated with 1 to 4 cycles of IV 177Lu-DOTATATE. The primary end point was radiological response after peptide receptor radionuclide therapy, and the secondary end point was improved quality of life using Karnofsky Performance Score and Eastern Cooperative Oncology Group score. RESULTS: In total, 16 subjects (10 males and 6 females) with a mean age of 55.68 ± 13.17 years (26-73 years) participated in the study. Of them, 8 patients were new HGG cases, and 8 patients had recurrent tumors. The participants' responses to treatments were complete remission in 12.5% of (n = 2), partial remission in 31.25% (n = 5), disease stability in 18.7% (n = 3), and disease progression in 37.5% (n = 6). In total, pretreatment and posttreatment Karnofsky Performance Score and Eastern Cooperative Oncology Group scores did not improved (P > 0.05). The patients were followed up from 1 month to 26 months (median, 3 months). CONCLUSIONS: This preliminary result suggests that peptide receptor radionuclide therapy using 177Lu-DOTATATE may be associated with positive effects in patients with HGGs (grade III-IV). However, this approach should be evaluated in a more homogeneous group of patients with more favorable performance status.


Assuntos
Glioma/patologia , Glioma/radioterapia , Receptores de Somatostatina/metabolismo , Adulto , Idoso , Complexos de Coordenação/uso terapêutico , Estudos de Viabilidade , Feminino , Glioma/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Octreotida/análogos & derivados , Octreotida/uso terapêutico , Compostos Organometálicos/uso terapêutico , Projetos Piloto , Estudos Prospectivos , Qualidade de Vida
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