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1.
Molecules ; 25(24)2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33321862

RESUMO

Several derivatives of benzoic acid and semisynthetic alkyl gallates were investigated by an in silico approach to evaluate their potential antiviral activity against SARS-CoV-2 main protease. Molecular docking studies were used to predict their binding affinity and interactions with amino acids residues from the active binding site of SARS-CoV-2 main protease, compared to boceprevir. Deep structural insights and quantum chemical reactivity analysis according to Koopmans' theorem, as a result of density functional theory (DFT) computations, are reported. Additionally, drug-likeness assessment in terms of Lipinski's and Weber's rules for pharmaceutical candidates, is provided. The outcomes of docking and key molecular descriptors and properties were forward analyzed by the statistical approach of principal component analysis (PCA) to identify the degree of their correlation. The obtained results suggest two promising candidates for future drug development to fight against the coronavirus infection.


Assuntos
Benzoatos/química , Inibidores de Cisteína Proteinase/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , /enzimologia , /antagonistas & inibidores , /química
2.
J Oleo Sci ; 69(11): 1427-1436, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33055444

RESUMO

This paper presents the results of a kinetic study performed between ninhydrin and a Ni(II) dipeptide complex under various conditions. The rate of formation of the imine adduct was measured spectrophotometrically both in plain aqueous media and in aqueous micellar media in which CTAB (cetyltrimethylammonium bromide) is used as the surfactant. These studies were carried out at pH 5 and over a temperature a range of 50 to 70°C. Studies were also conducted to elucidate the effect of some organic sodium salts on the rate of this reaction. In these studies, it was found that the formation of imine adduct followed a first-order kinetics with respect to [Ni(II)-Gly-Leu]+ in both aqueous and micellar medium. A fractional-order kinetics was observed with respect to ninhydrin, again in both aqueous and micellar media. Increase in the total concentration of CTAB from 0 to 40×10-3 mol dm-3 resulted in approximately two folds increase in the pseudo-first-order rate constant (kψ). The rate constant (kΨ) in micellar medium first increased with increase in CTAB concentration, reached a maximum value, and finally, with further increase in CTAB concentration, a decreasing effect was observed. Quantitative kinetic analysis of kψ-[CTAB] data was performed on the basis of the pseudo-phase model of the micelles. The rate profile in presence of CTAB suggests a cooperative effect in the enhanced formation of the imine adduct as is commonly found in enzyme catalyzed reactions. Addition of organic sodium salts (such as benzoate, salicylate and tosylate) enhanced the rate at lower concentrations but rates start to decrease at higher concentrations. This suggests that tightly binding organic counter-anions were the most effective. Viscosity of the reaction media seems to affect the kinetic behavior in micellar media.


Assuntos
Cetrimônio/química , Dipeptídeos/química , Iminas/química , Metais/química , Ninidrina/química , Tensoativos/química , Ânions/química , Benzoatos/química , Catálise , Concentração de Íons de Hidrogênio , Micelas , Fenômenos de Química Orgânica , Salicilatos/química , Espectrofotometria , Temperatura , Viscosidade , Água/química
3.
J Oleo Sci ; 69(7): 693-701, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612019

RESUMO

Fatty acid sugar esters are non-ionic surfactant active agents with excellent performance and many uses. This work is devoted to the synthesis of sugar esters by the esterification reaction of sugar with mixed carboxylicpalmitic anhydrides using resin Amberlyst-15 as heterogeneous acid catalyst. These anhydrides should be stable and react as acylating agents. Influence of different reaction parameters, such as the molar ratio (sucrose/anhydride), the type of solvent and the reaction time on the yield of the esterification reaction were studied. The esterification reaction of sucrose with mixed palmitic benzoic anhydride leads to a mixture of sucrose esters of palmitic acid with a good percentage of conversion. The mixed anhydride was both reactive and selective for the preparation of fatty acid ester.


Assuntos
Benzoatos/química , Ácidos Carboxílicos/química , Técnicas de Química Sintética/métodos , Ésteres/síntese química , Ácidos Graxos/síntese química , Ácido Palmítico/química , Sacarose/síntese química , Acilação , Catálise , Esterificação , Solventes , Estirenos , Tensoativos/síntese química , Fatores de Tempo
4.
J Chromatogr A ; 1622: 461120, 2020 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-32345440

RESUMO

The characterisation of the energetic properties of liquid crystals, i.e., esters with elongated molecules has been performed. The changes of the free energies of adsorption and absorption (dissolutions), ΔG, for liquid crystals have been estimated, based on the retention times of the centre of gravity of the elution peaks determined for the substances with defined physicochemical properties. The temperature-dependent van der Waals component of the free energy, [Formula: see text] , for a crystalline form of liquid crystal has been estimated by employing the Dorris-Gray approach. These approaches have been widened to mesophases, namely, the absorption(dissolution) of n-alkanes in the smectic B and nematic phases.


Assuntos
Benzoatos/química , Absorção Fisico-Química , Adsorção , Alcanos/química , Cromatografia Gasosa , Entropia , Temperatura
5.
PLoS One ; 15(3): e0228547, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32119679

RESUMO

Some excipients are currently available for the formulation of pharmaceutical suspensions. The objective of this study is to develop cheap and effective starch-based excipient that can be used as an effective alternative for the formulation of pharmaceutical suspensions. Carboxymethylated Plectranthus edulis, Vatke (P. edulis) [fam., Lamiaceae], starch was evaluated as a suspending agent in metronidazole benzoate suspensions in comparison with sodium carboxymethyl cellulose (NaCMC) at a concentration range of 1-4% (w/v). The resulting suspensions were evaluated for their sedimentation volume (%), degree of flocculation, rheology, redispersibility, and dissolution rate. Stability studies were performed for 3 months. The apparent viscosities of the formulations prepared with carboxymethylated P. edulis starch at reaction condition E (CMPS-E) was significantly lower than that of NaCMC (p < 0.05). The flowability of the suspensions, at all concentration levels of the suspending agents, were in the order of CMPS-E > NaCMC. AT 1% concentrations, carboxymethylated P. edulis starch (76 ± 1.5%) provided significantly higher (p < 0.05) sedimentation volume than NaCMC (40 ± 1.5%). At 3% and 4%, both gave comparable sedimentation volume (100%). Potassium dihydrogen phosphate (KH2PO4) employed as a flocculating agent significantly increased (p < 0.05) the sedimentation volume of the suspensions prepared with carboxymethylated P.edulis starch and NaCMC. The redispersibilities of CMPS-E were better than those of NaCMC. All suspensions showed a release of greater than 85% of drug within 1 h. The results of stability studies showed that all suspension formulations were stable. From the foregoing, it can be concluded that carboxymethylated P. edulis starch could be used as an alternative suspending agent.


Assuntos
Benzoatos/química , Composição de Medicamentos , Excipientes/química , Metronidazol/química , Plectranthus , Amido/química , Reologia , Suspensões
6.
Nat Commun ; 11(1): 405, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964883

RESUMO

Both of O-glycosides and nucleosides are important biomolecules with crucial rules in numerous biological processes. Chemical synthesis is an efficient and scalable method to produce well-defined and pure carbohydrate-containing molecules for deciphering their functions and developing therapeutic agents. However, the development of glycosylation methods for efficient synthesis of both O-glycosides and nucleosides is one of the long-standing challenges in chemistry. Here, we report a highly efficient and versatile glycosylation method for efficient synthesis of both O-glycosides and nucleosides, which uses glycosyl ortho-(1-phenylvinyl)benzoates as donors. This glycosylation protocol enjoys the various features, including readily prepared and stable donors, cheap and readily available promoters, mild reaction conditions, good to excellent yields, and broad substrate scopes. In particular, the applications of the current glycosylation protocol are demonstrated by one-pot synthesis of several bioactive oligosaccharides and highly efficient synthesis of nucleosides drugs capecitabine, galocitabine and doxifluridine.


Assuntos
Benzoatos/química , Técnicas de Química Sintética/métodos , Química Farmacêutica/métodos , Glicosídeos/síntese química , Nucleosídeos/síntese química , Produtos Biológicos/síntese química , Capecitabina/síntese química , Floxuridina/síntese química , Glicosilação , Estrutura Molecular
7.
Molecules ; 25(3)2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31979166

RESUMO

Two new xanthone derivatives, pestalotiones A (1) and B (2), one new diphenyl ketone riboside, pestalotione C (7), and one new diphenyl ether, pestalotione D (8), along with five known compounds isosulochrin dehydrate (3), 3,8-dihydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylate (4), isosulochrin (5), chloroisosulochrin (6), and pestalotether D (9), were isolated from the crude extract of the plant endophytic fungus Pestalotiopsis theae (N635). The structures of the new compounds were unambiguously deduced by HRESIMS and 1D/2D-NMR spectroscopic data. Compound 6 showed modest cytotoxicity against the HeLa cell line with an IC50 value of 35.2 µM. Compound 9 also showed cytotoxic to the HeLa and MCF-7 cell lines, with IC50 values of 60.8 and 22.6 µM, respectively. Additionally, compounds 1 and 2 exhibited antioxidant activity in scavenging DPPH radical with IC50 values of 54.2 and 59.2 µg/mL, respectively.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Benzoatos/química , Compostos de Bifenilo/química , Sobrevivência Celular/efeitos dos fármacos , Endófitos , Células HeLa , Humanos , Hidrocarbonetos Clorados/química , Concentração Inibidora 50 , Células MCF-7 , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Picratos/química
8.
Chem Asian J ; 15(4): 450-462, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-31895493

RESUMO

Carbohydrates contain numerous hydroxyl groups and sometimes amine functionalities which lead to a variety of complex structures. In order to discriminate each hydroxyl group for the synthesis of complex oligosaccharides, protecting group manipulations are essential. Although the primary role of a protecting group is to temporarily mask a particular hydroxyl/amino group, it plays a greater role in tuning the reactivity of coupling partners as well as regioselectivity and stereoselectivity of glycosylations. Several protecting groups offer anchimeric assistance in glycosylation. They also alter the solubility of substrates and thereby influence the reaction outcome. Since oligosaccharides comprise branched structures, the glycosyl donors and acceptors need to be protected with orthogonal protected groups that can be selectively removed one at a time without affecting other groups. This minireview is therefore intended to provide a discussion on new protecting groups for amino and hydroxyl groups, which have been introduced over last ten years in the field of carbohydrate synthesis. These protecting groups are also useful for synthesizing non-carbohydrate target molecules as well.


Assuntos
Oligossacarídeos/química , Benzoatos/química , Compostos de Benzilideno/química , Ésteres/química , Éter/química , Glicosídeos/química , Glicosilação , Oligossacarídeos/síntese química , Estereoisomerismo
9.
Nat Prod Res ; 34(12): 1663-1668, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30470138

RESUMO

A new phenolic compound (1) and together with 12 known compounds-eight flavonoids (2 ∼ 9), two phenolic compounds (10 and 11) and two benzoic acid (12 and 13)-were isolated from Phedimus middendorffianus (Maxim.). The structures of all compound were determined on the basis of spectroscopic (MS and NMR) analyses. Compounds 4, 5, 7 and 11 ∼ 13 were showed anti-proliferative activities against MCF-7 than PC-3 cell line. Also compound 12 and 13 showed the significant cytotoxic activities against two cancer cell lines, PC-3 and MCF-7.


Assuntos
Antineoplásicos/isolamento & purificação , Benzoatos/isolamento & purificação , Flavonoides/isolamento & purificação , Fenóis/isolamento & purificação , Sedum/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Benzoatos/química , Benzoatos/farmacologia , Linhagem Celular Tumoral , Flavonoides/química , Flavonoides/farmacologia , Humanos , Células MCF-7/efeitos dos fármacos , Estrutura Molecular , Células PC-3/efeitos dos fármacos , Fenóis/química , Fenóis/farmacologia
10.
Chemosphere ; 242: 125135, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31669991

RESUMO

The anionic form-dependent binding interaction of halo-phenolic substances with human transthyretin (hTTR) has been observed previously. This indicates that ionizable compounds should be the primary focus in screening potential hTTR disruptors. Here, the potential binding potency of halo-benzoic acids, halo-benzenesulfonic acids/sulfates and halo-phenylboronic acids with hTTR was determined and analyzed by competitive fluorescence displacement assay integrated with computational methods. The laboratorial results indicated that the three test groups of model compounds exhibited a distinct binding affinity to hTTR. All the tested halo-phenylboronic acids, some of the tested halo-benzoic acids and halo-benzenesulfonic acids/sulfates were shown to be inactive with hTTR. Other halo-benzoic acids and halo-benzenesulfonic acids/sulfates were moderate and/or weak hTTR binders. The binding affinity of halo-benzoic acids and halo-benzenesulfonic acids/sulfates with hTTR was similar. The low distribution ability of the model compounds from water to hTTR may be the reason why they exhibited the binding potency observed with hTTR. By introducing other highly hydrophobic compounds, we observed that the binding affinity between compounds and hTTR increased with increasing molecular hydrophobicity. Those results indicated that the highly hydrophobic halo-benzoic acids and halo-benzenesulfonic acids/sulfates may be high-priority hTTR disruptors. Finally, a binary classification model was constructed employing three predictive variables. The sensitivity (Sn), specificity (Sp), predictive accuracy (Q) values of the training set and validation set were >0.83, indicating that the model had good classification performance. Thus, the binary classification model developed here could be used to distinguish whether a given ionizable compound is a potential hTTR binder or not.


Assuntos
Benzenossulfonatos/química , Benzoatos/química , Ácidos Borônicos/química , Modelos Químicos , Pré-Albumina/química , Humanos , Fenóis , Pré-Albumina/metabolismo
11.
Luminescence ; 35(2): 284-291, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31762136

RESUMO

The direct determination of alogliptin benzoate (ALO) using fluorescence has not yet been accomplished because ALO cannot fluoresce naturally. Accordingly, it should be derivatized first with a fluorogenic reagent to enhance the sensitivity required for its bioanalysis. This method is the first spectrofluorimetric assay for ALO quantification exploiting the nucleophilic nature of its amino group to react with 4-chloro-7-nitrobenzofurazan (NBD-Cl) in borate buffer at pH 8.5 to produce a strong fluorescent compound that is excited at and emits at wavelengths 470 and 527 nm, respectively. Experimental variables concerning the conditions of reaction and fluorogenic intensity were carefully investigated and optimized. Linearity was from 1-250 ng ml-1 with a lower detection limit of 0.29 ng ml-1 and a lower quantification limit of 0.88 ng ml-1 . Validation of the current study was accomplished with mean per cent recovery of 100.62 ± 1.59 in tablets and 99.86 ± 0.82 in human plasma. Furthermore, the current method has been utilized in the bioanalysis of ALO in real rat plasma after oral administration with a simple specimen preparation. The developed method has proven to be a promising alternative method for ALO analysis in bioequivalence studies.


Assuntos
4-Cloro-7-nitrobenzofurazano/química , Benzoatos/sangue , Corantes Fluorescentes/química , Piperidinas/sangue , Espectrometria de Fluorescência , Uracila/análogos & derivados , Animais , Benzoatos/química , Benzoatos/farmacocinética , Humanos , Masculino , Estrutura Molecular , Piperidinas/química , Piperidinas/farmacocinética , Teoria Quântica , Ratos , Ratos Wistar , Espectrometria de Fluorescência/instrumentação , Uracila/sangue , Uracila/química , Uracila/farmacocinética
12.
Fitoterapia ; 140: 104442, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31790769

RESUMO

Averrhoa carambola L. (Oxalidaceae) was widely cultivated for fruits (star fruit), whereas the value of leaves remains to be discovered. Our study on the leaves yielded five flavan-3-ols (1-5) and two 2-diglycosyloxybenzoates. Their structures were determined by spectroscopic and chemical methods. Epicatechin-(5,6-bc)-4ß-(p-hydroxyphenyl)-dihydro-2(3H)-pyranone (1) and benzyl 2-ß-d-apiofuranosyl-(1 â†’ 6)-ß-d-glucopyranosyloxybenzoate (6) were new structures. 6-(S-2-Pyrrolidinone-5-yl)epicatechin (4) and 6-(R-2-pyrrolidinone-5-yl)epicatechin (5) were obtained as monomeric diastereomer for the first time and their absolute configurations were determined by electronic circular dichroism (ECD) computation. Epicatechin-(7,8-bc)-4α-(p-hydroxyphenyl)-dihydro-2(3H)-pyranone (2), epicatechin-(7,8-bc)-4ß-(p-hydroxyphenyl)-dihydro-2(3H)-pyranone (3), and methyl 2-ß-d-apiofuranosyl-(1 â†’ 6)-ß-d-glucopyranosyloxybenzoate (7) were not previously reported from the genus Averrhoa. Compounds 1-5 showed more potent 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS) radical cation and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities and ferric reducing antioxidant power (FRAP) than l-ascorbic acid. Meanwhile 1 and 3 exhibited lipase and α-glucosidase inhibitory activities, respectively. The results clarified the structures of flavan-3-ols and 2-diglycosyloxybenzoates in the leaves and their antioxidant, lipase, and α-glucosidase inhibitory activities.


Assuntos
Antioxidantes/química , Averrhoa/química , Benzoatos/química , Flavonoides/química , Folhas de Planta/química , Antioxidantes/isolamento & purificação , Benzoatos/isolamento & purificação , China , Flavonoides/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Lipase/antagonistas & inibidores , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação
13.
Chemistry ; 26(19): 4289-4296, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31834653

RESUMO

Cystobactamids belong to the group of arene-based oligoamides that effectively inhibit bacterial type IIa topoisomerases. Cystobactamid 861-2 is the most active member of these antibiotics. Most amide bonds present in the cystobactamids link benzoic acids with anilines and it was found that some of these amide bonds undergo chemical and enzymatic hydrolysis, especially the one linking ring C with ring D. This work reports on the chemical synthesis and biological evaluation of thirteen new cystobactamids that still contain the methoxyaspartate hinge. However, we exchanged selected amide bonds either by the urea or the triazole groups and modified ring A in the latter case. While hydrolytic stability could be improved with these structural substitutes, the high antibacterial potency of cystobactamid 861-2 could only be preserved in selected cases. This includes derivatives, in which the urea group is positioned between rings A and B and where the triazole is found between rings C and D.


Assuntos
Amidas/química , Compostos de Anilina/química , Antibacterianos/química , Bactérias/efeitos dos fármacos , Benzoatos/química , Triazóis/síntese química , Ureia/síntese química , Hidrólise , Estrutura Molecular , Triazóis/química , Ureia/química
14.
Sci Rep ; 9(1): 15791, 2019 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-31673001

RESUMO

Fluorescent proteins are used extensively in transgenic animal models to label and study specific cell and tissue types. Expression of these proteins can be imaged and analyzed using fluorescent and confocal microscopy. Conventional confocal microscopes cannot penetrate through tissue more than 4-6 µm thick. Tissue clearing procedures overcome this challenge by rendering thick specimens into translucent tissue. However, most tissue clearing techniques do not satisfactorily preserve expression of endogenous fluorophores. Using simple adjustments to the BABB (Benzoic Acid Benzyl Benzoate) clearing methodology, preservation of fluorophore expression can be maintained. Modified BABB tissue clearing is a reliable technique to clear skin and soft tissue specimens for the study of dermal biology, wound healing and fibrotic pathologies.


Assuntos
Benzoatos/química , Corantes Fluorescentes/química , Imageamento Tridimensional , Pele , Animais , Camundongos , Camundongos Transgênicos , Microscopia Confocal , Pele/citologia , Pele/metabolismo
15.
Sensors (Basel) ; 19(23)2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31775290

RESUMO

A surface-enhanced Raman scattering (SERS) tag is proposed for high-sensitivity detection of gibberellin A3 (GA3). Silver nanoparticles (AgNPs) were synthesized using citrate reduction. 4-Mercaptobenzoic acid (MBA) was used for the Raman-labeled molecules, which were coupled to the surface of the AgNPs using sulfydryls. MBA was coated with silica using the Stöber method to prevent leakage. GA3 antibodies were attached via the active functional groups N-Hydroxysuccinimide (NHS) and N-Ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC) to construct a novel immuno-AgNPs@SiO2 SERS tags. The captured SERS substrates were fabricated through Fe3O4 nanoparticles and gold nanoparticles (AuNPs) using chemical methods. These nanoparticles were characterized using ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering, Raman spectroscopy, transmission electron microscope (TEM), and X-ray diffraction (XRD). This immuno-AgNPs@SiO2 SERS tags has a strong SERS signal based on characterizations via Raman spectroscopy. Based on antigen-antibody reaction, the immuno-Au@Fe3O4 nanoparticles can capture the GA3 and AgNPs@SiO2 SERS tags. Due to the increasing number of captured nanoprobes, the SERS signal from MBA was greatly enhanced, which favored the sensitive detection of GA3. The linear equation for the SERS signal was y = -13635x + 202211 (R2 = 0.9867), and the limit of detection (LOD) was 10-10 M. The proposed SERS tags are also applicable for the detection of other food risk factors.


Assuntos
Benzoatos/química , Giberelinas/química , Ouro/química , Nanopartículas Metálicas/química , Dióxido de Silício/química , Prata/química , Compostos de Sulfidrila/química , Anticorpos/química , Técnicas Biossensoriais/métodos , Limite de Detecção , Análise Espectral Raman/métodos
18.
Molecules ; 24(21)2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31671554

RESUMO

Trastuzumab is an antibody used for the treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancers. Since trastuzumab is an internalizing antibody, two factors could play an important role in achieving high uptake and prolonged retention of radioactivity in HER2-positive tumors after radioiodination-residualizing capacity after receptor-mediated internalization and susceptibility to dehalogenation. To evaluate the contribution of these two factors, trastuzumab was radiolabeled using the residualizing reagent N-succinimidyl 4-guanidinomethyl-3-[*I]iodobenzoate ([*I]SGMIB) and the nonresidualizing reagent N-succinimidyl-3-[*I]iodobenzoate ([*I]SIB), both of which are highly dehalogenation-resistant. Paired-label uptake and intracellular retention of [125I]SGMIB-trastuzumab and [131I]SIB-trastuzumab was compared on HER2-expressing BT474 human breast carcinoma cells. Tumor uptake and normal tissue distribution characteristics for the two labeled conjugates were assessed in mice bearing BT474M1 xenografts. The internalization and intracellular retention of initially-bound radioactivity in BT474 cells was similar for the two labeled conjugates up to 4 h, but were significantly higher for [125I]SGMIB-trastuzumab at 6 and 24 h. Similarly, [*I]SGMIB labeling resulted in significantly higher uptake and retention of radioactivity in BT474M1 xenografts at all studied time points. Moreover, tumor-to-tissue ratios for [125I]SGMIB-trastuzumab were consistently higher than those for [131I]SIB-trastuzumab starting at 12 h postinjection. Thus, optimal targeting of HER2-positive breast cancers with a radioiodinated trastuzumab conjugate requires an acylation agent that imparts residualizing capacity in addition to high stability towards dehalogenation in vivo.


Assuntos
Benzoatos/química , Guanidina/análogos & derivados , Halogenação , Radioisótopos do Iodo/química , Trastuzumab/uso terapêutico , Acilação , Animais , Linhagem Celular Tumoral , Guanidina/química , Humanos , Camundongos , Controle de Qualidade , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Molecules ; 24(20)2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31640276

RESUMO

Recently polymer encapsulated surface-enhanced-Raman-scattering (SERS) probes with internal noble metal core-shell structure has found growing applications in biomedical applications. Here we studied the SERS spectra of Au@Ag-4MBA@PVP (4MBA: 4-mercaptobenzoic acid; PVP: polyvinylpyrrolidone) plasmonic nanoparticles produced from a chemical reduction method. By linking the atomic force microscope (AFM) with the homebuilt confocal Raman spectrometer thus to use AFM images as guidance, we realized the measurement of the SERS spectra from separated nanoparticles. We investigated the cases for single nanoparticles and for dimer structures and report several observed results including SERS spectra linearly scaled with laser power, abrupt boosting and abnormal shape changing of SERS spectra for dimer structures. Based on the finite element method simulation, we explained the observed ratio of SERS signals between the dimer structure and the single nanoparticle, and attributed the observed abnormal spectra to the photothermal effect of these plasmonic nanoparticles. Our study provides valuable guidance for choosing appropriate laser power when applying similar SERS probes to image biological cells.


Assuntos
Benzoatos/química , Ouro/química , Povidona/química , Prata/química , Compostos de Sulfidrila/química , Análise de Elementos Finitos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Microscopia de Força Atômica , Modelos Químicos , Análise Espectral Raman , Ressonância de Plasmônio de Superfície
20.
Molecules ; 24(20)2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31635211

RESUMO

Activation of the transcription factor liver X receptor (LXR) has beneficial effects on macrophage lipid metabolism and inflammation, making it a potential candidate for therapeutic targeting in cardiometabolic disease. While small molecule delivery via nanomedicine has promising applications for a number of chronic diseases, questions remain as to how nanoparticle formulation might be tailored to suit different tissue microenvironments and aid in drug delivery. In the current study, we aimed to compare the in vitro drug delivering capability of three nanoparticle (NP) formulations encapsulating the LXR activator, GW-3965. We observed little difference in the base characteristics of standard PLGA-PEG NP when compared to two redox-active polymeric NP formulations, which we called redox-responsive (RR)1 and RR2. Moreover, we also observed similar uptake of these NP into primary mouse macrophages. We used the transcript and protein expression of the cholesterol efflux protein and LXR target ATP-binding cassette A1 (ABCA1) as a readout of GW-3956-induced LXR activation. Following an initial acute uptake period that was meant to mimic circulating exposure in vivo, we determined that although the induction of transcript expression was similar between NPs, treatment with the redox-sensitive RR1 NPs resulted in a higher level of ABCA1 protein. Our results suggest that NP formulations responsive to cellular cues may be an effective tool for targeted and disease-specific drug release.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Benzoatos/farmacologia , Benzilaminas/farmacologia , Macrófagos/citologia , Animais , Benzoatos/química , Benzilaminas/química , Células Cultivadas , Composição de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Receptores X do Fígado/agonistas , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Nanopartículas , Poliésteres/química , Polietilenoglicóis/química , Cultura Primária de Células
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