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1.
Phys Chem Chem Phys ; 26(36): 23710-23721, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39229641

RESUMEN

Density functional theory (DFT) calculations at the TPSSh-D3(BJ)/def2-TZVP (SMD, water) level of theory were performed to understand the mechanism of redox-neutral depolymerization of four types of lignin-derived aryl ether dimers catalyzed by rhodium-terpyridine ([Rh]) and a binuclear Rh complex ([2Rh]). The cleavage of the Cß-O bond in the ß-O-4 model compound was initiated by the dehydrogenation of the alcohol moiety into a ketone intermediate, followed by the reductive cleavage of the ether bond, producing phenol and aromatic ketone products. The [Rh]-OH intermediate, generated by the interaction between the Rh-complex and NaOH, facilitated the transformation of the alcohol group to a CO group in the lignin model compound and subsequent H-transfer, selectively forming rhodium-H active species and the ketone intermediate. The [2Rh]-H complex exhibited high reactivity, with energy barriers for a rate-determining Cß-O bond breakage of 35.3 kcal mol-1. In contrast to 1-phenylethan-1-ol and H2, lignin itself acted as a good hydrogen source to generate [Rh]-H species. The transformation of ß-O-4 model compounds with the γ-OH group occurred via the elimination of the γ-OH group, reduction of the CC bond, and Cß-O bond cleavage steps. However, since lignin itself was unable to supply enough hydrogen to form [Rh]-H species, the aromatic products were obtained in low yields, as observed in the experiment.

2.
Inorg Chem ; 62(5): 2440-2455, 2023 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-36701493

RESUMEN

For phosphorescent materials, managing the triplet potential energy surface stands for controlling the phosphorescence quantum yield. However, due to the complexity and variability, the triplet potential energy surface can be managed with difficulty. In this work, a series of bimetallic Pt(II) complexes, namely Pt-1, Pt-1-1, Pt-1-2, Pt-2, Pt-3-5, and Pt-6-7, are employed as models to construct a relationship between the structures and triplet potential energy surfaces, aiming to achieve meaningful information to manage the triplet potential energy surface. On the basis of the results, it is observed that the triplet potential energy surface has an intimate connection with the structures of bimetallic Pt(II) complexes. In the case of the primordial Pt(II) complex, the triplet potential energy surface consists of two minimal points, illustrating various properties, which can largely affect the phosphorescence quantum yield. Once the intramolecular steric hindrance, restriction effect, and metallophilic interaction (Pt-Pd/Pd-Pd) are employed by tailoring the structures of primordial Pt(II) complexes, the triplet potential energy surface can be reconstructed via one minimal point-charactered short metal-metal distance, resulting in different photophysical properties. The relationship between the triplet potential energy surface and structure is essentially unveiled from the structural and electronic viewpoints. The conclusions originated from the structural and electronic investigations can be regarded as indicators to accurately and expediently predict the triplet potential energy surfaces of bimetallic Pt(II) complexes. The results presented here are helpful in addressing the designed strategies as they show that the triplet potential energy surfaces of bimetallic Pt(II) complexes can be properly tuned.

3.
Molecules ; 28(12)2023 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-37375142

RESUMEN

Operation lifetime, as an important parameter, determines the performance of phosphorescent organic light-emitting diodes (OLEDs). Unveiling the intrinsic degradation mechanism of emission material is crucial for improving the operation's lifetime. In this article, the photo-stabilities of tetradentate transition metal complexes, the popular phosphorescent materials, are explored by means of density functional theory (DFT) and time-dependent (TD)-DFT, aiming to illustrate the geometric signatures as important factors to control the photo-stabilities. Results indicate that for the tetradentate Ni(II), Pd(II), and Pt(II) complexes, the coordinate bonds of the Pt(II) complex exhibit stronger strength. It seems that the strengths of coordinate bonds are closely related to the atomic number of the metal center in the same group, which could be attributed to the various electron configurations. The effect of intramolecular and intermolecular interactions on ligand dissociation is also explored here. The large intramolecular steric hindrance and strong π-π interaction between the Pd(II) complexes caused by aggregation could effectively raise the energy barriers of the dissociation reaction, leading to an unfeasible reaction pathway. Moreover, the aggregation of Pd(II) complex can change the photo-deactivation mechanism as compared to that of monomeric Pd(II) complex, which is favored for avoiding the TTA (triplet-triplet annihilation) process.

4.
J Org Chem ; 87(17): 11888-11898, 2022 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-35976796

RESUMEN

An efficient one-pot reaction of propargylamides, isocyanides, and water catalyzed by zinc was developed for the rapid construction of 2-oxazolines with a wide functional group tolerance. The methylene-3-oxazoline was proven to play a vitally important role to start the tandem cascade transformation through unfunctionalized alkynes with sequential nucleophilic addition approaches of isocyanide and water. Notably, with a slight alteration of the reaction temperature and the addition of one molecule of water, various ß-amino amide derivatives were synthesized in good to excellent yields.


Asunto(s)
Amidas , Cianuros , Estructura Molecular , Agua , Zinc
5.
J Org Chem ; 87(1): 823-834, 2022 01 07.
Artículo en Inglés | MEDLINE | ID: mdl-34918940

RESUMEN

Structurally unique 2,2-disubstituted indolin-3-ones with a quaternary carbon center have been constructed through a novel C-C bond formation at the C3 position of Ugi N-acylamino amide adducts employing an organic base-mediated Dieckmann condensation. This facile, flexible protocol can be fine-tuned to construct drug-like pyrazino[1,2-a]indole fragments with the same quaternary carbon center only through the variation of the acid part in Ugi input. This novel and expeditious methodology has a broad scope and can rapidly generate the drug-like indolin-3-one core.


Asunto(s)
Amidas , Indoles , Carbono , Estructura Molecular
6.
Inorg Chem ; 61(24): 9162-9172, 2022 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-35666779

RESUMEN

Triplet potential energy surfaces are extremely important for phosphors because they are closely related to radiative and nonradiative decay processes. In this article, the correlations between the strctures and the triplet potential energy surfaces for Pt(II) complexes are investigated in detail with the help of density functional theory (DFT). The calculated results indicate that triplet hypersurface minima with different configurations, i.e., planar and bent, rely on the geometries of the platinum(II) complex. A bent configuration could cause an obvious decrease in the phosphorescence quantum yield, and an unusual low-lying triplet excited-state decay route is proposed. In addition, the extension of π-conjugation and addition of suitable substituents, for example arylboron, are promising strategies for changing the triplet hypersurface to achieve the minimum with a planar configuration, leading to a high phosphorescence quantum yield. Moreover, to predict the triplet hypersurface, a useful and simple strategy has been put forward. In our study, the relationship between the structure and the lowest-lying triplet potential energy surface of a Pt(II) complex is constructed, which is significant and meaningful for controlling the phosphorescence quantum yield to design high-performance phosphorescent materials used in the field of organic light-emitting diodes (OLEDs).

7.
J Clin Lab Anal ; 36(1): e24136, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34820903

RESUMEN

BACKGROUNDS: Free-wall rupture (FWR) has a high mortality rate. We aimed to find sensitive predictive indicators to identify high-risk FWR patients by exploring the predictive values of neutrophil percentage-to-albumin ratio (NPAR) and monocyte-to-lymphocyte ratio (MLR) on patients with acute myocardial infarction (AMI). METHODS: 76 FWR patients with AMI were collected, and then 228 non-CR patients with AMI were randomly selected (1:3 ratio) in this retrospective study. The independent influencing factors of FWR were evaluated by univariate and multivariate logistic regression analysis. The receiver-operating characteristic (ROC) curve analysis was applied to evaluate the predictive value of NPAR and MLR for FWR. RESULTS: According to the results of multivariate logistic regression analysis, emergency percutaneous coronary intervention (PCI) (OR = 0.27, 95% CI: 0.094-0.751, p = 0.012), angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) treatment (OR = 0.17, 95% CI: 0.044-0.659, p = 0.010), NPAR (OR = 2.69, 95% CI: 1.031-7.044, p = 0.043), and MLR (OR = 5.99, 95% CI: 2.09-17.168, p = 0.001) were the influencing factors of the FWR patients with AMI, independently. Additionally, the NPAR and MLR were the predictors of FWR patients, with AUC of 0.811 and 0.778, respectively (both p < 0.001). CONCLUSIONS: In summary, the emergency PCI and ACEI/ARB treatment were independent protective factors for FWR patients with AMI, while the increase of MLR and NPAR were independent risk factors. What's more, NPAR and MLR are good indicators for predicting FWR.


Asunto(s)
Albúminas/análisis , Leucocitos/fisiología , Infarto del Miocardio , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inflamación , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Infarto del Miocardio/fisiopatología , Pronóstico , Estudios Retrospectivos , Rotura
8.
Molecules ; 27(19)2022 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-36234785

RESUMEN

(1) Background: Colorectal cancer (CRC) is a common gastrointestinal malignancy, accounting for the second largest gastrointestinal tumor. MORC2, a newly discovered chromatin remodeling protein, plays an important role in the biological processes of various cancers. However, the potential mechanistic role of MORC2 in promoting proliferation of CRC carcinoma remains unclear. (2) Methods: The Cancer Genome Atlas database was analyzed using bioinformatics to obtain gene expression and clinical prognosis data. The cell proliferation was assessed by CCK8 and EdU assays, as well as xenograft. SA-beta-gal staining, Western blot, and ELISA assay were using to assess the cell senescence and potential mechanism. (3) Results: Our data showed that MORC2 expression was elevated in CRC patients. Depletion of MORC2 inhibited cellular proliferation both in vivo and in vitro. Further studies showed that the depletion of MORC2 enhanced p21 and p53 expression through decreasing HDAC4 and increasing pro-inflammatory factors IL-6 and IL-8, thus, promoting cellular senescence. (4) Conclusions: We concluded that increased MORC2 expression in CRC might play a critical role in tumorigenesis by regulating the cellular senescence, in addition, MORC2 could be a novel biomarker for clinical outcomes and prognosis and a treatment target for CRC.


Asunto(s)
Interleucina-6 , Proteína p53 Supresora de Tumor , Línea Celular Tumoral , Proliferación Celular/genética , Senescencia Celular/genética , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Proteínas Represoras/metabolismo , Factores de Transcripción/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo
9.
J Org Chem ; 85(18): 11626-11634, 2020 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-32835476

RESUMEN

Understanding the mechanism of the catalytic reaction is an effective way to design new high-performance catalysts. The mechanisms of alkyne/olefin hydrogenations catalyzed by a nonclassical Co-N2 catalyst are explored by ab initio molecular dynamics simulations and density functional theory calculations. From the calculated results, the hydrogenation mechanisms, i.e., molecular or atomic mechanisms, can be effectively controlled via employing the different interaction between the catalyst and substrates. The origination of excellent selectivity toward E-olefins for the Co-N2 catalyst is also taken into account with the help of investigating the olefin hydrogenation process. The mechanism indicates that the negligible energy barrier of rotation is the main reason for highly selective semihydrogenation of a Co-N2 catalyst, which leads to the trans-olefin formation. These investigations may provide some useful information and guidelines on the current understanding of the hydrogenation reaction and designing the high-performance catalysts.

10.
Phys Chem Chem Phys ; 22(29): 16905-16913, 2020 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-32671372

RESUMEN

Understanding the mechanism of a catalytic reaction is of fundamental importance not only scientifically but also technologically to the design of high-performance catalysts. In this work, the mechanisms of 1-phenyl-1-propyne and cis-ß-methylstyrene hydrogenations catalyzed by Cu55 and ligand-coated Cu55 are explored in detail by means of density functional theory (DFT). The calculated results indicate that the semihydrogenation selectivity of the catalyst can be effectively controlled by employing a suitable ligand. That is, the PCy3 and PPh3 ligands used to coat Cu55 can largely raise the energy barrier of the rate-determining step for cis-ß-methylstyrene hydrogenation. By the study of energy decomposition analysis (EDA) and charge density difference, it can be found that the deformation energies of the substrate fragments play a crucial role in the energy barriers of the rate-determining steps. The large hindrance effect of the ligands is beneficial for improving the semihydrogenation selectivity of the catalysts. This study provides significant information for future catalyst design and on the physical origin of the phosphine ligand-coated nanoparticle catalysis for semihydrogenation.

11.
Phys Chem Chem Phys ; 22(11): 6222-6230, 2020 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-32129367

RESUMEN

Unveiling the reaction mechanism is significant for developing high-performance catalysts. In this paper, a series of precisely controlled PdxM147-x (M = Cu, Pt, Au, Rh, Ru) dendrimer encapsulated nanoparticles (DENs) has been successfully synthesized. The mechanisms of PdxM147-x as catalysts for Suzuki cross-coupling reactions were investigated by combining experimental and theoretical methods. The experimental results indicate that Pd74Cu73 DEN shows similar activity to Pd147 DEN and excellent substrate adaptability under mild reaction conditions. Moreover, the Cu component can play an important role in tuning the catalytic activity of PdxCu147-x DEN. Density functional theory (DFT) calculations illustrate that the similar activities of the Pd147 and Pd74Cu73 DENs originate from the comparable energy barriers of the rate-determining steps. The partial density of states (PDOS) and electron density differences demonstrate that Cu decreases the intensities of the valence orbitals of the top and edge Pd atoms and weakens orbital interactions between the intermediates and Pd74Cu73 DEN, leading to low desorption energies of the products. This work can provide a promising strategy to reduce the cost of Pd catalysts in Suzuki cross-coupling reactions.

12.
Phys Chem Chem Phys ; 21(5): 2764-2770, 2019 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-30666322

RESUMEN

For phosphorescent emitters, the rigidity of the geometry is a crucial indicator, which can directly determine the non-radiative decay rate. In this article, density functional theory (DFT) calculations were performed to investigate the influence of the small substituent groups on the rigidities of tridentate Pt(ii) complexes in detail. The calculated results indicate that the small substituent groups can serve as geometric controllers to suppress the structural distortion on going from the ground state (S0) to the lowest-lying triplet excited state (T1) (Jahn-Teller distortion). For instance, when electron-donating substituent groups, including -NH2, -N(CH3)2 and -OCH3, were employed, the rigidities of the corresponding Pt(ii) complexes can be effectively enhanced because the highest occupied molecular orbital (HOMO)-HOMO-1 energy gaps could be increased. Different from the electron-donating substituent groups, electron-withdrawing substituent groups, i.e., -NO2 and -COCH3, can cause a negligible change in HOMO and HOMO-1 energies during the S0 → T1 transition process, and therefore, for Pt-NO2 and Pt-COCH3, no Jahn-Teller distortion occurs. According to the calculated results, the rigidities of tridentate Pt(ii) complexes could be raised via tuning the energies of the frontier molecular orbital (FMO) with the help of small substituent groups.

13.
Phys Chem Chem Phys ; 21(33): 18105-18118, 2019 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-31396604

RESUMEN

With the emergence of drug-resistant Plasmodium falciparum, the treatment of malaria has become a significant challenge; therefore, the development of antimalarial drugs acting on new targets is extremely urgent. In Plasmodium falciparum, type II nicotinamide adenine dinucleotide (NADH) dehydrogenase (NDH-2) is responsible for catalyzing the transfer of two electrons from NADH to flavin adenine dinucleotide (FAD), which in turn transfers the electrons to coenzyme Q (CoQ). As an entry enzyme for oxidative phosphorylation, NDH-2 has become one of the popular targets for the development of new antimalarial drugs. In this study, reliable motion trajectories of the NDH-2 complex with its co-factors (NADH and FAD) and inhibitor, RYL-552, were obtained by comparative molecular dynamics simulations. The influence of cofactor binding on the global motion of NDH-2 was explored through conformational clustering, principal component analysis and free energy landscape. The molecular interactions of NDH-2 before and after its binding with the inhibitor RYL-552 were analyzed, and the key residues and important hydrogen bonds were also determined. The results show that the association of RYL-552 results in the weakening of intramolecular hydrogen bonds and large allosterism of NDH-2. There was a significant positive correlation between the angular change of the key pocket residues in the NADH-FAD-pockets that represents the global functional motion and the change in distance between NADH-C4 and FAD-N5 that represents the electron transfer efficiency. Finally, the possible non-competitive inhibitory mechanism of RYL-552 was proposed. Specifically, the association of inhibitors with NDH-2 significantly affects the global motion mode of NDH-2, leading to widening of the distance between NADH and FAD through cooperative motion induction; this reduces the electron transfer efficiency of the mitochondrial respiratory chain. The simulation results provide useful theoretical guidance for subsequent antimalarial drug design based on the NDH-2 structure and the respiratory chain electron transfer mechanism.


Asunto(s)
Antimaláricos/química , Cetonas/química , NADH Deshidrogenasa/antagonistas & inhibidores , Plasmodium falciparum/enzimología , Proteínas Protozoarias/antagonistas & inhibidores , Proteínas Protozoarias/química , Quinolinas/química , Transporte de Electrón , Flavina-Adenina Dinucleótido/química , Enlace de Hidrógeno , Modelos Moleculares , Estructura Molecular , NAD/química , NADH Deshidrogenasa/química , Oxidación-Reducción , Unión Proteica , Relación Estructura-Actividad , Termodinámica
14.
Opt Express ; 26(8): 10435-10451, 2018 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-29715981

RESUMEN

Evidence of water reflectance saturation in extremely turbid media is highlighted based on both field measurements and satellite data corrected for atmospheric effects. This saturation is obvious in visible spectral bands, i.e., in the blue, green and even red spectral regions when the concentration of suspended particulate matter (SPM) reaches then exceeds 100 to 1000 g.m-3. The validity of several bio-optical semi-analytical models is assessed in the case of highly turbid waters, based on comparisons with outputs of the Hydrolight radiative transfer model. The most suitable models allow to reproduce the observed saturation and, by inversion, to retrieve information on the SPM mass-specific inherent optical properties.

15.
Chemphyschem ; 19(17): 2200-2207, 2018 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-29923369

RESUMEN

In this article, the photo-deactivation mechanism of dual emission of a neutral iridium (III) complex is explored by using density function theory (DFT) and time-dependent density function theory (TD-DFT) calculations. To explore the phosphorescence quantum yield of the iridium (III) complex, the radiative decay constant of each emission excited state was computed by TD-DFT calculations, including spin-orbit coupling (SOC). In these calculations, factors such as the transition dipole moments, energy gaps, and SOC elements between the emission states and singlet excited states are taken into account in the evaluation of the radiative decay constants. Additionally, the non-radiative decay is revealed by considering the temperature-independent and the temperature-dependent non-radiative processes. The computational results indicate that the order of the two emission excited states can exert a significant effect on the phosphorescence quantum yield, which is beneficial for understanding the properties of photo-deactivation of phosphorescent emitters.

16.
Chemphyschem ; 17(24): 4149-4157, 2016 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-27717179

RESUMEN

Aromatic sulfonyl groups have attracted increasing interest due to their unique electronic features. In this article, a series of IrIII complexes bearing fluorinated phenylsulfonyl groups were evaluated by density functional theory and time-dependent density functional theory methods. To explore their phosphorescence efficiencies, factors that determine the radiative decay rate constant, kr , and the nonradiative decay rate constant, knr , were computed. As demonstrated by the results, complex 4, which has fluorinated phenylsulfonyl groups at the 5-positions of the phenyl rings for all three C^N ligands, was found to have the highest phosphorescence efficiencies with the largest kr and smallest knr values among these complexes. Moreover, it was found to exhibit significantly blueshifted behavior relative to complex 1 and emits in the blue region, and thus, it can serve as a highly efficient blue emitter for application in organic light-emitting diodes. These findings successfully illustrated the structure-properties relationship and provided valuable information for the development of future highly efficient blue-emitting phosphors.

17.
Chemphyschem ; 17(1): 69-77, 2016 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-26515923

RESUMEN

In this article, the influence of the tert-butyl unit on the photodeactivation pathways of Pt[O^N^C^N] (O^N^C^N=2-(4-(3,5-di-tert-butylphenyl)-6-(3-(pyridin-2-l)phenyl) pyridin-2-yl)phenolate) is investigated by DFT/TDDFT calculations. To further explore the factors that determine the radiative processes, the transition dipole moments of the singlet excited states, spin-orbit coupling (SOC) matrix elements, and energy gaps between the lowest triplet excited states and singlet excited states are calculated. As demonstrated by the results, compared with Pt-3, Pt-1 and Pt-2 have larger SOC matrix elements between the lowest triplet excited states and singlet excited states, an indicator that they have faster radiative decay processes. In addition, the SOC matrix elements between the lowest triplet excited states and ground states are also computed to elucidate the temperature-independent non-radiative decay processes. Moreover, the temperature-dependent non-radiative decay mechanisms are also explored via the potential energy profiles.


Asunto(s)
Compuestos Organoplatinos/química , Piridinas/química , Transferencia de Energía , Luminiscencia , Modelos Químicos , Estructura Molecular , Temperatura
18.
J Phys Chem A ; 120(34): 6813-21, 2016 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-27517617

RESUMEN

In this study, density functional theory (DFT) and time-dependent DFT were employed to elucidate the photo-deactivation mechanisms of (C^N)Pt(O^O) complexes 1-4 (where C^N = 2-phenylpyridine derivatives, O^O = dipivolylmethanoate). To make thorough understanding of the radiative decay, the singlet-triplet splitting energies ΔE(Sn-T1) (n = 1, 2, 3, 4, ...), transition dipole moment µ(Sn) for S0-Sn transitions and the spin-orbit coupling (SOC) matrix elements ⟨T1|HSOC|Sn⟩ were all calculated. Moreover, the spin-orbit coupling between T1 and S0 ⟨T1|HSOC|S0⟩ and Huang-Rhys factors were calculated to estimate the temperature-independent nonradiative decay processes. Meanwhile, the thermal deactivation via metal-centered (3)MC was described to analyze the temperature-dependent nonradiative decay processes. As a result, the effective SOC interaction between the lowest triplet and singlet excited states successfully rationalize why complexes 1 and 3 have higher radiative decay rate constant than that of complex 2, while the larger ⟨T1|HSOC|S0⟩ and lower energy barrier for thermal deactivation in 3 reasonably explains why 3 has larger nonradiative rate than that of 1 and 2. Consequently, it can be concluded that it is the ⟨T1|HSOC|S0⟩ and thermal population of (3)MC that account for the nonemissive behavior of (C^N)Pt(O^O) complexes, and controlling π-conjugation is an efficient method for tuning phosphorescence properties of transition-metal complexes.

19.
Int J Biol Macromol ; 257(Pt 1): 128620, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38070804

RESUMEN

Inflammation plays a key role in the progression of choroidal neovascularization (CNV). Regular intravitreal injection of anti-VEGF medication is required for many patients to sustain eye condition as CNV always recurs due to persistent chronic inflammation in the retina and choroid. Marine bromophenols (BDB) have been widely studied due to their diverse bioactivities, including anti-inflammatory effect, though the mechanism of which remained unclear. Our study demonstrated that BDB could restricted endothelial cells' function and suppressed choroidal explants both in vitro and in vivo without out affecting the cells viability. BDB also significantly reduced numerous inflammatory cytokines in both raw cells and choroidal tissue, including IL-1ß, IL-6, TNF-α, IL-4 and MMP-9. Moreover, we demonstrated that BDB down regulated phosphorylation of NF-κB p65 in the raw cells. By Co-IP assay, HUWE1 was found to be bound with BDB and the binding location was at sequences position 4214. When overexpressed HUWE1 in HUVECs, the suppression of endothelial cells' function by BDB became more significant. Taken together, the findings in this study showed that BDB suppressed endothelial cells' function and choroidal neovascularization by targeting HUWE1 through NF-κB pathway, which suggested that BDB could be a potential therapeutic candidate in treating chronic inflammation in choroidal neovascularization.


Asunto(s)
Bencidinas , Neovascularización Coroidal , FN-kappa B , Humanos , Animales , Ratones , FN-kappa B/metabolismo , Células Endoteliales/metabolismo , Transducción de Señal , Neovascularización Coroidal/tratamiento farmacológico , Neovascularización Coroidal/metabolismo , Inflamación/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo
20.
Curr Protein Pept Sci ; 25(10): 797-813, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38919078

RESUMEN

Platinum (II) drugs, including cisplatin, carboplatin, and oxaliplatin, have achieved significant clinical success in cancer treatment. However, their clinical application has been greatly hindered by various adverse factors, such as non-specific activation and drug resistance. Compared with Pt(II) drugs, the axial ligands within Pt(IV) compounds can improve the pharmacokinetic properties, selectivity, and biological activity, implementing alternative cytotoxic mechanisms beyond DNA cross-linking and partially overcoming drug resistance. The controlled conversion of Pt(IV) prodrugs into Pt(II) agents at the tumor site has been extensively explored internationally. In this review, Pt(IV) prodrug modification strategies are first summarized, and the development of the predominant external and internal photosensitizers is listed. Finally, three representative photoreduction mechanisms and strategies for developing corresponding Pt(IV) prodrugs are discussed. This work provides constructive instruction for the subsequent molecular design of Pt(IV) prodrugs.


Asunto(s)
Antineoplásicos , Neoplasias , Fármacos Fotosensibilizantes , Profármacos , Profármacos/química , Profármacos/farmacología , Profármacos/uso terapéutico , Profármacos/farmacocinética , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Neoplasias/metabolismo , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/farmacología , Compuestos Organoplatinos/química , Compuestos Organoplatinos/farmacología , Compuestos Organoplatinos/uso terapéutico , Animales , Cisplatino/farmacología , Cisplatino/química , Cisplatino/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos
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