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1.
Dalton Trans ; 53(41): 16941-16955, 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39351607

RESUMO

This study reports the development of new probes RR1 ((1E)-1-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene)ethyl thiosemicarbazone) and RR2 ((1E)-1-(1-(6-bromo-2-oxo-2H-chromen-3-yl)ethylidene)phenyl thiosemicarbazone), which selectively showed fluorescence turn 'OFF' response towards Cu2+ and Al3+. Further, complexes of RR1-Cu2+ and RR2-Al3+ acted as chemosensors for the detection of L-amino acids. RR1-Cu2+ selectively detected L-arginine (fluorescence turn 'ON'), and RR2-Al3+ selectively detected L-glutamic acid (fluorescence turn 'ON'). The existence of the fluorophore-quencher complexes RR1-Cu2+ and RR2-Al3+ was confirmed by theoretical studies. Further, the chemosensors RR1-Cu2+ and RR2-Al3+ have three possible structural isomers (RR1-Cu2+-L-arginine - A, B and C) and (R2-Al3+-L-glutamic acid - D, E and F), as confirmed by theoretical studies. In vitro bio-imaging of the probes (RR1 and RR2), complexes (RR1-Cu2+ and RR2-Al3+) and complexes associated with L-arginine (RR1-Cu2+-L-arginine) and L-glutamic acid (R2-Al3+-L-glutamic acid) was performed in the MDA-MB-231 cell line using their IC50 concentrations. In addition, in vivo live cell imaging studies were conducted using C. elegans as the model organism.


Assuntos
Arginina , Cobre , Cumarínicos , Corantes Fluorescentes , Ácido Glutâmico , Bases de Schiff , Arginina/química , Corantes Fluorescentes/química , Ácido Glutâmico/análise , Ácido Glutâmico/química , Cobre/química , Animais , Humanos , Cumarínicos/química , Bases de Schiff/química , Alumínio/química , Alumínio/análise , Caenorhabditis elegans/metabolismo , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Linhagem Celular Tumoral , Imagem Óptica , Estrutura Molecular
2.
Top Curr Chem (Cham) ; 382(4): 31, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39382816

RESUMO

In recent years, the near-infrared (NIR) light-emitting materials have attracted increasing attention due to the broad application prospects in the fields of military industry, aerospace, lighting, display and wearable devices. As the transition metal complexes, platinum(II) complexes have been shown to emit luminescence efficiently in NIR organic light-emitting diodes because of the unique d8 electron structure. This structure ensures that the platinum(II) complex molecules exhibit a high planarity, variety of excited states, and strong intermolecular interactions. This review summarizes the research progress of deep red to NIR organic light-emitting materials based on platinum(II) complexes in recent years and provides a certain reference for the further design and synthesis of NIR platinum(II) complex luminescent materials with superior performance.


Assuntos
Complexos de Coordenação , Platina , Platina/química , Complexos de Coordenação/química , Raios Infravermelhos , Substâncias Luminescentes/química , Luminescência , Compostos Organoplatínicos/química , Compostos Organoplatínicos/síntese química
3.
Inorg Chem ; 63(41): 19167-19178, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39352230

RESUMO

Lomefloxacin hydrochloride (LMFX) and sodium salicylate (SS) are important targets for real-time detection due to their widespread uses in daily life; accurate and portable monitoring of LMFX and SS is crucial for human health concerns accordingly. Developing a precise and smart platform for determination of the above analytes remains a significant challenge. Herein, a high-sensitivity platform incorporating a luminescence electrospinning film, self-designed smart-phone app, and portable 3D printing device has been developed to identify LMFX and SS. In this work, two heterometallic coordination polymers with two-dimensional layer structures have been synthesized based on 2,2'-oxidiacetic acid ligand (H2oda), namely, [LnPb(oda)2(CH3COO)]n [Ln = Eu (IMU-1); Tb (IMU-2)]. IMU-1 and IMU-2 were ratio-dependent luminescence probes, which could selectively and sensitively sense with LMFX and SS, respectively. Additionally, the synthesized electrospinning films incorporating IMU-1 and IMU-2 were employed to identify LMFX and SS. Both films could rapidly photograph and color-capture through a portable 3D printing device, along with a self-designed smart-phone app that enabled convenient and quick determination of the concentrations of the above analytes. Remarkably, the mechanism exploration indicated that electron transfer from ligands to analytes affected the antenna effect and further utilized the intrinsic luminescence of analytes along with the luminescence quenching of Ln3+ ions. Furthermore, a strategy for constructing ratio-based fluorescent probes by exploiting the luminescence of analytes and Ln3+ ions in host coordination polymers is proposed. This work provides a new insight by combining luminescence probes, portable devices, and a smart-phone app for real-time detection of drugs and food additives.


Assuntos
Fluoroquinolonas , Polímeros , Smartphone , Salicilato de Sódio , Fluoroquinolonas/análise , Polímeros/química , Salicilato de Sódio/química , Salicilato de Sódio/análise , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Estrutura Molecular , Limite de Detecção
4.
Anal Chem ; 96(41): 16362-16369, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39358909

RESUMO

Enhancing the electrochemiluminescence (ECL) properties of polycyclic aromatic hydrocarbons (PAHs) is a significant topic in the ECL field. Herein, we elaborately chose PAH derivative luminophore 1,3,6,8-tetrakis(p-benzoic acid)pyrene (H4TBAPy) as the organic ligand to synthesize a new Ru-complex-free ECL-active metal-organic framework Dy-TBAPy. Interestingly, Dy-TBAPy exhibited a more brilliant ECL emission and higher ECL efficiency than H4TBAPy aggregates. On the one hand, TBAPy luminophores were assembled into rigid MOF skeleton via coordination bonds, which not only enlarged the distance between pyrene cores to eliminate the aggregation-caused quenching (ACQ) effect but also obstructed the intramolecular motions of TBAPy to diminish the nonradiative relaxation, thus realizing a remarkable coordination-enhanced ECL. On the other hand, the ultrahigh porosity of Dy-TBAPy was beneficial to the diffusion of electrons, ions, and coreactant (S2O82-) in the skeleton, which efficiently boosted the excitation of interior TBAPy luminophores and led to a high utilization ratio of TBAPy, further improving ECL properties. More intriguingly, the ECL intensity of the Dy-TBAPy/S2O82- system was about 4.1, 87.0-fold higher than those of classic Ru(bpy)32+/TPrA and Ru(bpy)32+/S2O82- systems. Considering the aforementioned fabulous ECL performance, Dy-TBAPy was used as an ECL probe to construct a supersensitive ECL biosensor for microRNA-21 detection, which showed an ultralow detection limit of 7.55 aM. Overall, our study manifests that coordinatively assembling PAHs into MOFs is a simple and practicable way to improve ECL properties, which solves the ACQ issue of PAHs and proposes new ideas for developing highly efficient Ru-complex-free ECL materials, therefore providing promising opportunities to fabricate high-sensitivity ECL biosensors.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Medições Luminescentes , Estruturas Metalorgânicas , Pirenos , Estruturas Metalorgânicas/química , Pirenos/química , Técnicas Eletroquímicas/métodos , Técnicas Biossensoriais/métodos , Humanos , Complexos de Coordenação/química , Limite de Detecção
5.
Int J Mol Sci ; 25(19)2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39409123

RESUMO

The antiproliferative and antibacterial activities of thiosemicarbazones increase markedly with the presence of metal ions. One of the factors determining the activity of metal thiosemicarbazone complexes is the coordination structure. In this study, the biological effects of new antimony (III) and bismuth (III) thiosemicarbazone complexes with different binding modes and geometrical structures were demonstrated. Three new complexes, with the formulae {[SbCl3(µ2-S-Hacptsc)(η1-S-Hacptsc)], 2/3H2O,1/3CH2Cl2}, {[SbCl3(κ2-S,N-Hacpmtsc)(η1-S-Hacpmtsc)2CH2Cl2]}, and{[BiCl3(η1-S-Hbzmtsc)3]·C2H5OH}, where Hacptsc: acetophenone thiosemicarbazone, Hacpmtsc: acetophenone-N-methyl thiosemicarbazone, Hbzmtsc: benzaldehyde-N-methyl thiosemicarbazone) were elucidated by different methods and deeply analyzed in accordance with their structure by X-ray structure analysis and Atoms-In-Molecules topological analysis. This analysis provided a deeper understanding of the coordination spheres of the Sb/Bi complexes. For instance, the first reported two binding modes of the same ligand are observed in a single crystal structure of antimony (III) halide complexes. Additionally, in one of the complexes, a solid-to-solid phase transition was detected and analyzed in detail. Those complexes, very unique in terms of their geometry, have also been tested for their in vitro cytotoxic activity against human adenocarcinoma cervical cancer (HeLa) cells, whereas antimony (III) complex 1is the most active complex of this study. Further, the antibacterial activity of the complexes has been screened against two Gram-negative (Pseudomonas aeruginosa and Escherichia coli) and two Gram-positive (Staphylococcus epidermidis and Staphylococcus aureus) pathogenic bacteria. From the results, it is found that all the complexes exhibited significant activity against the Gram-negative pathogenic bacteria.


Assuntos
Antibacterianos , Antimônio , Complexos de Coordenação , Testes de Sensibilidade Microbiana , Tiossemicarbazonas , Tiossemicarbazonas/química , Tiossemicarbazonas/farmacologia , Tiossemicarbazonas/síntese química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Humanos , Antimônio/química , Antimônio/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Bismuto/química , Bismuto/farmacologia , Cristalografia por Raios X , Modelos Moleculares
6.
Int J Mol Sci ; 25(19)2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39409141

RESUMO

New bismuth (III) complexes with acetophenone-4-methyl-3-thiosemicarbazone (L) and halogens (Cl and Br) in both bridging and terminal positions have been synthesized and structurally characterized using single-crystal X-ray diffraction. The pure complexes (Cl or Br) were found to be highly isostructural, which motivated our attempts to create solid solutions of these complexes. A series of such compounds was prepared using various procedures and stoichiometries. A method for determining the mutual concentrations of different halogens, based on the positions of selected peaks in powder diffraction patterns, was tested and compared with other methods.


Assuntos
Bismuto , Complexos de Coordenação , Tiossemicarbazonas , Tiossemicarbazonas/química , Bismuto/química , Cristalografia por Raios X/métodos , Complexos de Coordenação/química , Acetofenonas/química , Halogenação , Modelos Moleculares , Estrutura Molecular , Difração de Pó , Difração de Raios X/métodos
7.
Int J Mol Sci ; 25(19)2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39409159

RESUMO

Research in the field of metallodrugs is continually increasing. However, it is often limited by the poor solubility in water of the metal complexes. To try to overcome this problem, the two new ligands bis-(sodium 3-methoxy-5-sulfonate-salicylaldehyde)thiocarbohydrazone (bis-TCH, Na2H4L1) and bis-(sodium 3-methoxy-5-sulfonate-salicylaldehyde)carbohydrazone (bis-CH, Na2H4L2) were synthesized and characterized, both achieving high solubility in water. The speciation of the ligands and their coordinating behaviour towards the biologically relevant Cu(II) and Zn(II) ions were studied spectroscopically and potentiometrically, determining the pKas of the ligands and the formation constants of the complex species. The monometallic and bimetallic Cu(II) and Zn(II) complexes were isolated, and the single-crystal X-ray structure of [Cu2(NaHL1)(H2O)7].3.5H2O was discussed. Finally, preliminary studies of the in vitro cytotoxic properties of the new compounds were started on normal (Hs27) and cancer (U937) cell lines. bis-TCH was able to induce a growth inhibition effect between 40% and 45% in both cell lines; bis-CH did not produce a reduction in cell viability in Hs27 cells but revealed mild antiproliferative activity after 72 h of treatment in U937 cancer cells (GI50 = 46.5 ± 4.94 µg/mL). Coordination of the Cu(II) ions increased the toxicity of the compounds, while, in contrast, Zn(II) complexes were not cytotoxic.


Assuntos
Complexos de Coordenação , Cobre , Hidrazonas , Solubilidade , Água , Zinco , Zinco/química , Cobre/química , Humanos , Hidrazonas/química , Hidrazonas/farmacologia , Hidrazonas/síntese química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Água/química , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Ligantes , Sobrevivência Celular/efeitos dos fármacos , Cristalografia por Raios X
8.
Molecules ; 29(19)2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39407603

RESUMO

Structural DNA nanotechnology is an emerging field and is expected to be used for various applications in materials science. In this study, we designed a DNA tensegrity triangle to accommodate the bipyridine complexes with metal ions (Ni2+ and Fe2+) at the center of the space within the triangle. A metal-bipyridine-incorporated DNA tensegrity triangle was crystalized, and the presence of metals within it was confirmed through X-ray crystal structure analysis. A signal of the anomalous dispersion effect derived from metal was observed in the center of the DNA triangle.


Assuntos
Complexos de Coordenação , DNA , DNA/química , Complexos de Coordenação/química , Cristalografia por Raios X , Níquel/química , Modelos Moleculares , Metais/química , Nanotecnologia/métodos , Conformação de Ácido Nucleico , Ferro/química , Cristalização
9.
Inorg Chem ; 63(41): 19105-19116, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39352869

RESUMO

The necessity to move away from conventional antibiotic therapy has sparked interest in antimicrobial peptides (AMPs). One fascinating example is human CCL-28 chemokine produced by acinar epithelial cells in the salivary glands. It can also be released into the oral cavity with saliva, playing a crucial role in oral protection. The C-terminal domain of CCL-28 possesses antifungal and antibacterial properties, which are likely linked to membrane disruption and enzyme leakage. Studies suggest that AMPs can become more potent after they have bound Cu(II) or Zn(II). In many cases, these ions are essential for maximizing effectiveness by altering the peptides' physicochemical properties, such as their local charge or structure. The examined peptide binds Cu(II) and Zn(II) ions very effectively, forming equimolar complexes. Metal ion binding affinity, coordination mode, and antimicrobial activity strongly depend on the pH of the environment. Coordination modes have been proposed based on the results of potentiometric titrations, spectroscopic studies (UV-visible, electron paramagnetic resonance and circular dichroism at different path lengths), and mass spectrometry. The antimicrobial properties of the Cu(II) and Zn(II) complexes with the C-terminal fragment of CCL-28 chemokine have been assessed against fungal and bacterial strains, demonstrating exceptional activity against Candida albicans at pH 5.4. Moreover, the complex with Zn(II) ions shows the same activity against theStreptococcus mutans bacterium as chloramphenicol, a commonly used antibiotic. Cyclic voltammetry proposed a probable antimicrobial mechanism of the studied Cu(II) complex through the formation of reactive oxygen species, which was also confirmed by tests with ascorbic acid in UV-vis and fluorescence spectroscopic studies.


Assuntos
Complexos de Coordenação , Cobre , Testes de Sensibilidade Microbiana , Zinco , Zinco/química , Zinco/farmacologia , Cobre/química , Cobre/farmacologia , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Humanos , Candida albicans/efeitos dos fármacos , Antifúngicos/farmacologia , Antifúngicos/química , Antifúngicos/síntese química , Química Bioinorgânica
10.
Inorg Chem ; 63(41): 19140-19155, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39361042

RESUMO

Despite advances in Ir(III) and Ru(II) photosensitizers (PSs), their lack of selectivity for cancer cells has hindered their use in photodynamic therapy (PDT). We disclose the synthesis and characterization of two pairs of Ir(III) and Ru(II) polypyridyl complexes bearing two ß-carboline ligands (N^N') functionalized with -COOMe (L1) or -COOH (L2), resulting in PSs of formulas [Ir(C^N)2(N^N')]Cl (Ir-Me: C^N = ppy, N^N' = L1; Ir-H: C^N = ppy, N^N' = L2) and [Ru(N^N)2(N^N')](Cl)2 (Ru-Me: N^N = bpy, N^N' = L1; Ru-H: N^N = bpy, N^N' = L2). To enhance their selectivity toward cancer cells, Ir-H and Ru-H were coupled to a bombesin derivative (BN3), resulting in the metallopeptides Ir-BN and Ru-BN. Ir(III) complexes showed higher anticancer activity than their Ru(II) counterparts, particularly upon blue light irradiation, but lacked cancer cell selectivity. In contrast, Ir-BN and Ru-BN exhibited selective photocytoxicity against prostate cancer cells, with a lower effect against nonmalignant fibroblasts. All compounds generated ROS and induced severe mitochondrial toxicity upon photoactivation, leading to apoptosis. Additionally, the ability of Ir-Me to oxidize NADH was demonstrated, suggesting a mechanism for mitochondrial damage. Our findings indicated that the conjugation of metal PSs with BN3 creates efficient PDT agents, achieving selectivity through targeting bombesin receptors and local photoactivation.


Assuntos
Antineoplásicos , Bombesina , Carbolinas , Irídio , Fotoquimioterapia , Fármacos Fotossensibilizantes , Neoplasias da Próstata , Rutênio , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/síntese química , Humanos , Irídio/química , Irídio/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Masculino , Rutênio/química , Rutênio/farmacologia , Carbolinas/química , Carbolinas/farmacologia , Carbolinas/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Bombesina/química , Bombesina/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Estrutura Molecular , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos
11.
Int J Mol Sci ; 25(19)2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39408673

RESUMO

Chiral pincer complexes, characterized by their rigid tridentate coordination framework, have emerged as powerful catalysts in asymmetric synthesis. This review provides a comprehensive overview of recent advancements in the development of chiral pincer-type ligands and their corresponding transition metal complexes. We highlight the latest progress in their application across a range of catalytic asymmetric reactions, including the (transfer) hydrogenation of polar and non-polar bonds, hydrophosphination, alkynylation, Friedel-Crafts reactions, enantioselective reductive cyclization of alkynyl-tethered cyclohexadienones, enantioselective hydrosilylation, as well as Aza-Morita-Baylis-Hillman reactions. The structural rigidity and tunability of chiral pincer complexes enable precise control over stereoselectivity, resulting in high enantioselectivity and efficiency in complex molecular transformations. As the field advances, innovations in ligand design and the exploration of new metal centers are expected to expand the scope and utility of these catalysts, bearing significant implications for the synthesis of enantioenriched compounds in pharmaceuticals, materials science, and beyond.


Assuntos
Complexos de Coordenação , Catálise , Estereoisomerismo , Complexos de Coordenação/química , Ligantes , Hidrogenação , Ciclização , Elementos de Transição/química , Estrutura Molecular
12.
ACS Appl Mater Interfaces ; 16(42): 56777-56788, 2024 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-39380145

RESUMO

In recent decades, researchers have focused on developing less toxic and more precise cancer therapies. Carbon nanodots (CDs) are among the most promising technologies due to their high biocompatibility, tunable fluorescence, and ability to facilitate photothermal and photodynamic therapy. This study explores the synthesis and characterization of two CDs conjugated with Salphen metal complexes, namely, CDs-PEG-M1 and CDs-PEG-M2, through Sonogashira coupling. Their interaction with G-quadruplex DNA structures (G4s), motifs largely involved in cancer development, was evaluated using various spectroscopic techniques. The results indicate that CDs-PEG-M1 exhibits greater effectiveness in stabilizing G4 structures compared to the metal complex alone or nonfunctionalized CDs. This enhanced stabilization suggests that CDs-PEG-M1 could reduce the concentration of the metal complex needed for potential antitumor applications, thereby minimizing side effects on nontarget tissues. When tested on breast cancer models (MDA-MB-231 as a triple-negative model and MCF-7 as a HER-2 positive model) and on a healthy cell line (HDFa), the CDs-PEG-M1 conjugate reduced cell viability in a concentration- and time-dependent manner, showing greater potency and selectivity against cancer cells compared to virgin CDs and the free M1 complex. This synergistic anticancer effect, driven by the interaction with G4 structures and reactive oxygen species production, underscores the potential of CDs-PEG-M1 as a targeted nanotheranostic tool.


Assuntos
Antineoplásicos , Carbono , Quadruplex G , Níquel , Humanos , Carbono/química , Carbono/farmacologia , Níquel/química , Níquel/farmacologia , Quadruplex G/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/química , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Pontos Quânticos/química , Polietilenoglicóis/química , Células MCF-7 , Proliferação de Células/efeitos dos fármacos , Fenilenodiaminas
13.
J Med Chem ; 67(20): 18512-18525, 2024 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-39365559

RESUMO

Noninvasive and real-time nitric oxide (NO) visualization in vivo is still a challenge. Herein, we constructed a series of NO-responsive magnetic resonance imaging (MRI) contrast agents Gd1b-e by modifying Gd-DO3A using a bis-pyridyl-ethylamine side chain as a signal-amplifying moiety and o-phenylenediamine as a NO-responsive linker. It was found that Gd1b, d, and e can form macromolecular ternary complexes (Gd-Zn2+-HSA) with high longitudinal relaxivity (r1) (12.2-16.2 mM-1 s-1). Once reacting with NO, the o-phenylenediamine linker was hydrolyzed to produce a small molecular Gd complex with sharply decreased r1 (4.7-6.3 mM-1 s-1). Among them, Gd1d with a desirable pharmacokinetic profile (t1/2 = 5.91 h) could clearly distinguish the ischemia-reperfusion (IR) liver with excessive NO in rats. Meanwhile, the temporarily reduced amount of NO in the IR liver and brain by the NO scavenger 2-phenyl-4,4,5,5-tetramethylimidazoline-3-oxide-1-oxyl could enhance the signal of Gd1d, suggesting anticipated NO-responsive property. This research offers a new avenue for insight into the NO spatiotemporal property in multiple IR organs.


Assuntos
Meios de Contraste , Gadolínio , Fígado , Imageamento por Ressonância Magnética , Óxido Nítrico , Traumatismo por Reperfusão , Animais , Humanos , Masculino , Ratos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Meios de Contraste/química , Meios de Contraste/farmacocinética , Complexos de Coordenação/química , Complexos de Coordenação/farmacocinética , Complexos de Coordenação/síntese química , Gadolínio/química , Fígado/metabolismo , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Óxido Nítrico/metabolismo , Ratos Sprague-Dawley , Traumatismo por Reperfusão/diagnóstico por imagem , Traumatismo por Reperfusão/metabolismo , Zinco/química , Zinco/metabolismo , Imidazóis/química , Imidazóis/metabolismo
14.
Inorg Chem ; 63(42): 19769-19782, 2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39389034

RESUMO

Targeting inflammation and the molecules involved in the inflammatory process could be an effective cancer prevention and therapy strategy. Therefore, the use of anti-inflammatory strategies, such as NSAIDs and metal-based drugs, has become a promising approach for preventing and treating cancer by targeting multiple pathways involved in tumor progression. The present work describes new phosphane gold(I) complexes derived from nonsteroidal anti-inflammatory drugs as multitarget drugs against colon cancer. The antiproliferative effect of the most active complexes, [Au(L3)(JohnPhos)] (3b), [Au(L4)(CyJohnPhos)] (4a) and [Au(L4)(JohnPhos)] (4b) against colon cancer cells (Caco2-/TC7) seems to be mediated by the inhibition of the enzyme cyclooxygenase-1/2, modulation of reactive oxygen species levels by targeting thioredoxin reductase (TrxR) activity, and induction of apoptosis in cancer cells. Additionally, the three complexes exhibit high selectivity index values toward noncancerous cells. The research highlights the importance of maintaining cellular redox balance and the role of TrxR in cancer cell survival.


Assuntos
Anti-Inflamatórios não Esteroides , Antineoplásicos , Apoptose , Proliferação de Células , Neoplasias do Colo , Complexos de Coordenação , Ouro , Espécies Reativas de Oxigênio , Humanos , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Proliferação de Células/efeitos dos fármacos , Ouro/química , Ouro/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Ensaios de Seleção de Medicamentos Antitumorais , Ciclo-Oxigenase 2/metabolismo , Tiorredoxina Dissulfeto Redutase/antagonistas & inibidores , Tiorredoxina Dissulfeto Redutase/metabolismo , Estrutura Molecular , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 1/química , Sobrevivência Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Relação Estrutura-Atividade , Células CACO-2 , Compostos Organoáuricos/farmacologia , Compostos Organoáuricos/química , Compostos Organoáuricos/síntese química
15.
Drug Dev Res ; 85(7): e22265, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39358925

RESUMO

Four lanthanide complexes with 8-hydroxyquinoline-2-aldehyde-2-hydrazinopyridine (H-L1), 8-hydroxyquinoline-2-aldehyde-2-hydrazimidazole (H-L2): [Sm(L1)2][Sm(L1)(NO3)3]·CHCl3·2CH3OH (1), [Gd(L1)2][Gd(L1)(NO3)3]·CHCl3·2CH3OH (2), [Sm(L2)(NO3)2]2·CH3OH (3), and [Eu(L2)(NO3)2]2·CH3OH (4) were synthesized and characterized. In vitro cytotoxicity evaluation showed that the ligands and four lanthanide complexes exhibited cytotoxicity to the five tested tumor cell lines. Among them, complex 1 showed the best antiproliferative activity against NCI-H460 tumor cells. Mechanistic studies demonstrated that complex 1 arrested the cell cycle of NCI-H460 cells in G1 phase and induced mitochondria-mediated apoptosis, which resulted in the loss of mitochondrial membrane potential, enhanced intracellular Ca2+ levels and reactive oxygen species generation. In addition, complex 1 affected the expression levels of intracellular apoptosis-related proteins and activated the caspase-3/9 in NCI-H460 cells. Therefore, complex 1 is a potential anticancer agent.


Assuntos
Antineoplásicos , Apoptose , Proliferação de Células , Oxiquinolina , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Oxiquinolina/farmacologia , Oxiquinolina/química , Linhagem Celular Tumoral , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Elementos da Série dos Lantanídeos/farmacologia , Elementos da Série dos Lantanídeos/química , Espécies Reativas de Oxigênio/metabolismo , Ciclo Celular/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
16.
Inorg Chem ; 63(42): 19607-19618, 2024 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-39384553

RESUMO

SufU, a component of the SufCDSUB Fe-S cluster biosynthetic system, serves as a Zn-dependent sulfur-carrying protein that delivers inorganic sulfur in the form of cysteine persulfide from SufS to SufBCD. To understand this sulfur delivery mechanism, we studied the X-ray crystal structure of SufU and its sulfur-carrying state (persulfurated SufU) and performed functional analysis of the conserved amino acid residues around the Zn sites. Interestingly, sulfur-carrying SufU with Cys41-persulfide (Cys41-Sγ-Sδ-) exhibited a unique Zn coordination structure, in which electrophilic Sγ is ligated to Zn and nucleophilic/anionic Sδ is bound to distally conserved Arg125. This structure is distinct from those of other Cys-persulfide-Sδ-ligated metals of metalloproteins, such as hybrid cluster proteins and SoxAX. Functional analysis of SufU variants with Zn-ligand and Arg125 substitutions revealed that both Zn and Arg125 are critical for the function of SufU with SufS. The Zn-persulfide structure of SufU provides insight into the sulfur-transfer process, suggesting that persulfide-Sδ- is stabilized via bridging by Zn and Arg125 of SufU.


Assuntos
Cisteína , Proteínas Ferro-Enxofre , Sulfetos , Enxofre , Zinco , Cisteína/química , Cisteína/análogos & derivados , Zinco/química , Enxofre/química , Proteínas Ferro-Enxofre/química , Proteínas Ferro-Enxofre/metabolismo , Sulfetos/química , Sulfetos/metabolismo , Modelos Moleculares , Cristalografia por Raios X , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/metabolismo , Dissulfetos
17.
Chem Commun (Camb) ; 60(83): 11940-11943, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39352495

RESUMO

The development of theranostic agents for radiopharmaceuticals based on therapeutic alpha emitters marks an important clinical need. We describe a strategy for the development of theranostic agents of this type via the functionalization of the ligand with the diagnostic radionuclide fluorine-18. An analogue of macropa, an 18-membered macrocyclic chelator with high affinity for alpha therapeutic radiometals, was synthesized and its complexation properties with metal ions were determined. The new macropa-F ligand was used for quantitative radiometal complexation with lead-203 and bismuth-207, as surrogates for their alpha-emitting radioisotopes. As a diagnostic partner, a radiofluorinated macropa ligand was used for quantitative bismuth(III) and lead(II) complexation. All fluorine-18 and radiometal complexes are highly stable in human serum over several days. This study presents a new proof-of-principle approach for developing theranostic agents based on alpha-emitting radionuclides and fluorine-18.


Assuntos
Bismuto , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Ligantes , Humanos , Radioisótopos de Flúor/química , Bismuto/química , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Complexos de Coordenação/farmacologia , Quelantes/química , Quelantes/síntese química , Chumbo/química , Partículas alfa/uso terapêutico , Compostos Macrocíclicos/química , Compostos Macrocíclicos/síntese química
18.
Arh Hig Rada Toksikol ; 75(3): 159-171, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39369326

RESUMO

Neutral bis(amino acidato)copper(II) [Cu(aa)2] coordination compounds are the physiological species of copper(II) amino acid compounds in blood plasma taking the form of bis(l-histidinato)copper(II) and mixed ternary copper(II)-l-histidine complexes, preferably with l-glutamine, l-threonine, l-asparagine, and l-cysteine. These amino acids have three functional groups that can bind metal ions: the common α-amino and carboxylate groups and a side-chain polar group. In Cu(aa)2, two coordinating groups per amino acid bind to copper(II) in-plane, while the third group can bind apically, which yields many possibilities for axial and planar bonds, that is, for bidentate and tridentate binding. So far, the experimental studies of physiological Cu(aa)2 compounds in solutions have not specified their complete geometries. This paper provides a brief review of my group's research on structural properties of physiological Cu(aa)2 calculated using the density functional theory (DFT) to locate low-energy conformers that can coexist in aqueous solutions. These DFT investigations have revealed high conformational flexibility of ternary Cu(aa)2 compounds for tridentate or bidentate chelation, which may explain copper(II) exchange reactions in the plasma and inform the development of small multifunctional copper(II)-binding drugs with several possible copper(II)-binding groups. Furthermore, our prediction of metal ion affinities for Cu2+ binding with amino-acid ligands in low-energy conformers with different coordination modes of five physiological Cu(aa)2 in aqueous solution supports the findings of their abundance in human plasma obtained with chemical speciation modelling.


Assuntos
Aminoácidos , Cobre , Cobre/química , Cobre/sangue , Aminoácidos/química , Aminoácidos/sangue , Humanos , Complexos de Coordenação/química , Complexos de Coordenação/sangue
19.
Artif Cells Nanomed Biotechnol ; 52(1): 529-550, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39462870

RESUMO

Lens culinaris L., has been widely recognized for its medical applications. LC-ESI-TOF-MS identified 22 secondary metabolites including phenolics, flavonoids, and anthocyanidin glycosides among its total extract (LCTE). The study aimed to apply LCTE as a biogenic material for reducing and capping the silver nanoparticles (LC-AgNPs). The ynthesized LC-AgNPs were characterized using different techniques. The UV absorption was observed at λmax 379 nm. LC-AgNPs were spherical, with 19.22 nm average size. The face cubic centre nature was demonstrated by HR-TEM and XRD. The LC-AgNPs were then evaluated for their anticancer and antimicrobial potentials. LC-AgNPs showed an extremely potent cytotoxic activity against MCF-7, HCT-116 and HepG2 cell lines (IC50= 0.37, 0.35 and 0.1 µg/mL, respectively). LC-AgNPs induced significant apoptotic effects in the three examined cancer cell lines. LC-AgNPs resulted in sequestration of cells in G1 phase of the cell cycle in both MCF-7 and HCT-116 cells, meanwhile it trapped cells at the G2 phase in HepG2 cells. Moreover, the antimicrobial activity of LC-AgNPs was highly confirmed against Klebsiella pneumoniae and Acinetobacter baumannii. Molecular docking study designated Kaempferol-3-O-robinoside-7-O-rhamnoside and Quercetin-3-D-xyloside as the topmost LCTE active constituents that caused inhibition of both Bcl-2 and IspC cancer targets in combination with the produced silver nanoparticles.


Assuntos
Antineoplásicos , Flavonoides , Química Verde , Nanopartículas Metálicas , Simulação de Acoplamento Molecular , Proteínas Proto-Oncogênicas c-bcl-2 , Prata , Humanos , Nanopartículas Metálicas/química , Prata/química , Prata/farmacologia , Flavonoides/química , Flavonoides/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Apoptose/efeitos dos fármacos , Células Hep G2 , Células MCF-7 , Células HCT116 , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química
20.
Top Curr Chem (Cham) ; 382(4): 35, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39453566

RESUMO

Epoxides are class of cyclic ether and have been extensively used in petrochemicals and pharmaceuticals industries as raw materials. Due to this reasons, development of the synthetic strategy of epoxides are getting enormous interest among the research chemists. In terms of "development of the synthetic strategy", the use of a catalyst, especially, Schiff base-based complex is of potential interest due to alternative easy routes and significant advances in metal-mediated pathways giving rise to diverse degree of substrate-reagent interactions. In addition, the synthetic strategy that follows the 12 principles of green chemistry, particularly (i) reduce the use of organic solvent, especially toxic solvents, and (ii) increasing the use of catalysts to obtain selective and quick processes in terms of atom economy, are of great attention now a days. The present review encompasses the Schiff base-based molybdenum complexes as green catalyst in the epoxidation reaction. Molybdenum complexes have grown interest owing to lower cost, environmental protection and commercialization as well as its abundance in different metalloenzymes. On the other hand, molybdenum complexes speed up the O-O bond break of tert-butylhydroperoxide (TBHP); as a result, it accelerates the oxygen transfer process from TBHP to the olefin. This review mainly focused on the catalytic activity of molybdenum-based Schiff base complexes for the epoxidation reaction in water/solvent free condition.


Assuntos
Complexos de Coordenação , Compostos de Epóxi , Química Verde , Molibdênio , Bases de Schiff , Bases de Schiff/química , Catálise , Molibdênio/química , Compostos de Epóxi/química , Complexos de Coordenação/química
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