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1.
Acta Crystallogr C Struct Chem ; 75(Pt 12): 1658-1665, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31802756

RESUMO

Because of its versatile coordination modes and strong coordination ability, the mercaptoacetic acid substituted 1,2,4-triazole 2-{[5-(pyridin-2-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}acetic acid (H2L) was synthesized and characterized. Treatment of H2L with cobalt and nickel acetate afforded the dinuclear complexes {µ-3-[(carboxylatomethyl)sulfanyl]-5-(pyridin-2-yl)-4H-1,2,4-triazol-4-ido-κ2N1,N5:N2,O}bis[aqua(methanol-κO)cobalt(II)] methanol disolvate, [Co2(C9H6N4O2S)2(CH3OH)2(H2O)2]·2CH3OH (1), and {µ-3-[(carboxylatomethyl)sulfanyl]-5-(pyridin-2-yl)-4H-1,2,4-triazol-4-ido-κ2N1,N5:N2,O}bis[diaquanickel(II)] methanol disolvate dihydrate, [Ni2(C9H6N4O2S)2(H2O)4]·2CH3OH·2H2O (2), respectively. Complex 1 crystallized in the monoclinic space group P21/c, while 2 crystallized in the tetragonal space group I41/a. Single-crystal X-ray diffraction studies revealed that H2L is doubly deprotonated and acts as a tetradentate bridging ligand in complexes 1 and 2. For both of the obtained complexes, extensive hydrogen-bond interactions contribute to the formation of their three-dimensional supermolecular structures. Hirshfeld surface analysis was used to illustrate the intermolecular interactions. Additionally, the urease inhibitory activities of 1, 2 and H2L were investigated against jack bean urease, where the two complexes revealed strong urease inhibition activities.


Assuntos
Acetatos/química , Cobalto/farmacologia , Complexos de Coordenação/química , Níquel/farmacologia , Compostos Organometálicos/química , Tioglicolatos/farmacologia , Urease/antagonistas & inibidores , Urease/química , Cobalto/química , Cristalografia por Raios X , Ligações de Hidrogênio , Ligantes , Modelos Moleculares , Níquel/química , Tioglicolatos/química
2.
Int J Biol Macromol ; 136: 476-485, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31220490

RESUMO

In this work, we reported a novel "one-pot" strategy for preparation of chitosan-coated carbon nanotubes (CNTs) composites via a combination of Diels-Alder (DA) reaction and mercaptoacetic acid locking imine (MALI) reaction for the first time. To evaluate the adsorption characteristics, the as-prepared samples were applied to remove copper ions (Cu2+) from aqueous solution. The effects of contact time, solution pH, temperature and initial Cu2+ concentration on the adsorption of Cu2+ onto the as-prepared samples were investigated. The chitosan modified CNTs composites showed high affinity and fast kinetics for the adsorption of Cu2+ ions, and adsorption capacity of the composites was found to be 2 times that of pristine CNTs. Adsorption kinetics and thermodynamic indicated a spontaneous and endothermic nature of the adsorption of Cu2+ on the surface of chitosan-coated CNTs composites, kinetically obeyed the pseudo-second-order model. Equilibrium data could be best described by the Langmuir isotherm model, with a maximum monolayer adsorption capacity of 115.84 mg/g. In view of the extensive applicability of DA chemistry and MALI reaction, different carbon nanomaterials based composites with various functional groups could be fabricated and applicable to different fields such as environmental catalysis and biomedicine.


Assuntos
Quitosana/química , Cobre/química , Cobre/isolamento & purificação , Nanotubos de Carbono/química , Tioglicolatos/química , Poluentes Químicos da Água/química , Poluentes Químicos da Água/isolamento & purificação , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Modelos Moleculares , Conformação Molecular , Temperatura Ambiente
3.
Int J Biol Macromol ; 133: 382-390, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31002909

RESUMO

Keratin has been attracting interest due to its stability against enzymatic degradation thereby allowing more predictable degradation profile for tissue regeneration applications. While the efficacy of keratin has been demonstrated in different tissue models, there has been no systematic study to investigate and compare the different routes of keratin extraction from human hair. Here, we compared the four commonly used extraction methods and highlighted both physical and chemical differences in the extracted keratin. Keratin was extracted from human hair using one of four common agents, namely, sodium sulfide, peracetic acid, urea and thioglycolic acid. Whereas no specific trend was observed, the keratin extracted through peracetic acid method had significantly different properties. It resulted in lowest yield of 52 µg/mL and low crystallinity but the protein formed aggregates with highest hydrodynamic average size of around 283 nm compared to the other three methods. However, despite greater aggregation, keratin extracted from peracetic acid method exhibited secondary structural conformation similar to thioglycolic acid method. All the four extracted keratin promoted cellular proliferation of osteoblasts compared to the uncoated surface. These results provide new insight into the extraction of keratin from human hair with implications for its use as a biomaterial.


Assuntos
Fracionamento Químico/métodos , Cabelo/química , Queratinas/isolamento & purificação , Humanos , Queratinas/química , Tamanho da Partícula , Ácido Peracético/química , Estrutura Secundária de Proteína , Tioglicolatos/química
4.
Drug Dev Ind Pharm ; 45(5): 754-766, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30640559

RESUMO

Current research work was conducted to synthesize Thiol modified arabinoxylan and its application in fabrication of hydrogel. Thioglycolic acid was esterified with arabinoxylan to prepare Thiolatedarabinoxylan. Appearance of peak at 2533.34 cm-1 in FTIR and thiol content showed successful thiolation. The pH-dependent Thiolatedarabinoxylan/acrylic acid (TAX/AA) hydrogels of perindopril erbumine were prepared via free-radical co-polymerization. Perindopril erbumine (PE) was employed as model drug. Different batches with different feed ratio of TAX, AA, and MBA were prepared and their influence on swelling, solvent penetration, and consequent drug release was investigated. Swelling coefficients increased with increase in pH. TAX/AA hydrogels were characterized by Fourier-transform infrared spectroscopy (FT-IR), Thermal Analysis (TA), X-Ray diffraction (XRD), and scanning electron microscope (SEM). Dissolution studies were performed at pH 1.2 and 7.4 in which drug release showed direct correlation with TAX and AA ratio. In vivo studies showed that Cmax of TAX-co-AA based hydrogel was 81.57 ± 0.35 ng/ml which was maintained for a longer time after its administration. All the results of in vivo studies were significant and TAX-co-AA based hydrogel enhances the bioavailability of perindopril erbumine.


Assuntos
Acrilatos/química , Portadores de Fármacos/química , Perindopril/farmacocinética , Xilanos/química , Animais , Disponibilidade Biológica , Liberação Controlada de Fármacos , Hidrogéis/química , Concentração de Íons de Hidrogênio , Perindopril/administração & dosagem , Plantago/química , Coelhos , Tioglicolatos/química , Xilanos/isolamento & purificação
5.
Drug Metab Dispos ; 47(2): 104-113, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30442650

RESUMO

Lesinurad [Zurampic; 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)], a selective inhibitor of uric acid reabsorption transporters approved for the treatment of gout, is a racemate of two atropisomers. The objective of this investigation was to evaluate the stereoselectivity of metabolism, the inhibitory potency on kidney uric acid reabsorption transporters (URAT1 and OAT4), and the clinical pharmacokinetics of the lesinurad atropisomers. Incubations with human liver microsomes (HLM), recombinant CYP2C9, and recombinant CYP3A4 were carried out to characterize the stereoselective formation of three metabolites: M3 (hydroxylation), M4 (a dihydrodiol metabolite), and M6 (S-dealkylation). The formation of M3 in HLM with atropisomer 1 was approximately twice as much as that with atropisomer 2, whereas formation of M4 with atropisomer 1 was 8- to 12-fold greater than that with atropisomer 2. There were no significant differences in the plasma protein binding among lesinurad and the atropisomers. Following oral administration of 400 mg lesinurad once daily for 14 days to healthy human volunteers, the systemic exposure (C max at steady state and area under the concentration-time curve from time zero to the time of dosing interval) of atropisomer 1 was approximately 30% lower than that of atropisomer 2, whereas renal clearance was similar. In vitro cell-based assays using HEK293 stable cells expressing URAT1 and OAT4 demonstrated that atropisomer 2 was approximately 4-fold more potent against URAT1 than atropisomer 1 and equally active against OAT4. In conclusion, lesinurad atropisomers showed stereoselectivity in clinical pharmacokinetics, metabolism, and inhibitory potency against URAT1.


Assuntos
Transportadores de Ânions Orgânicos/antagonistas & inibidores , Proteínas de Transporte de Cátions Orgânicos/antagonistas & inibidores , Reabsorção Renal/efeitos dos fármacos , Tioglicolatos/farmacologia , Triazóis/farmacologia , Ácido Úrico/metabolismo , Uricosúricos/farmacologia , Administração Oral , Adulto , Gota/tratamento farmacológico , Células HEK293 , Voluntários Saudáveis , Humanos , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Microssomos Hepáticos , Pessoa de Meia-Idade , Transportadores de Ânions Orgânicos/metabolismo , Transportadores de Ânions Orgânicos Sódio-Independentes/antagonistas & inibidores , Transportadores de Ânions Orgânicos Sódio-Independentes/metabolismo , Proteínas de Transporte de Cátions Orgânicos/metabolismo , Estereoisomerismo , Relação Estrutura-Atividade , Tioglicolatos/química , Tioglicolatos/metabolismo , Tioglicolatos/uso terapêutico , Triazóis/química , Triazóis/metabolismo , Triazóis/uso terapêutico , Ácido Úrico/sangue , Ácido Úrico/urina , Uricosúricos/química , Uricosúricos/metabolismo , Uricosúricos/uso terapêutico , Adulto Jovem
6.
ACS Sens ; 3(11): 2335-2342, 2018 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-30350589

RESUMO

Detection of explosive residues in soil and postblast debris is an important issue in sensor design for environmental and criminological purposes. An easy-to-use and low-cost gold nanoparticle (AuNP)-based colorimetric sensor was developed for the determination of nitroaromatic explosives, i.e., trinitrotoluene (TNT) and tetryl, capable of analyte detection at picomolar (pM) levels. The sensor nanoparticles were synthesized by functionalizing the negatively charged thioglycolic acid (TGA)-modified AuNPs with positively charged (±)- trans-1,2-diaminocyclohexane (DACH) at a carefully calculated pH. The working principle of the sensor is charge-transfer (CT) interaction between the electron-rich free amino (-NH2) group of DACH and the electron-deficient -NO2 groups of TNT/tetryl, added to possible nanoparticle agglomerization via electrostatic interaction of TNT-Meisenheimer anions with more than one cationic DACH-modified AuNP. The limit of detection (LOD) and limit of quantification (LOQ) of the sensor were 1.76 pM and 5.87 pM for TNT and 1.74 pM and 5.80 pM for tetryl, respectively. TNT, tetryl, and tetrytol, extracted from a nitroaromatic explosive-contaminated soil sample, were determined with the proposed sensor, yielding good recoveries. The sensor could be selectively applied to various mixtures of TNT with common energetic materials such as RDX, HMX, and PETN. Additionally, common soil ions (Cl-, NO3-, SO42-, K+, Mg2+, Ca2+, Cu2+, Fe2+, Fe3+, and Al3+) as well as detergents, sugar, sweeteners, acetylsalicylic acid (aspirin), caffeine, and paracetamol-based painkiller drugs, which may be used as camouflage materials for explosives, either had no adverse effects or removable interferences on the detection method. The developed method was statistically validated against a GC-MS literature method.


Assuntos
Compostos de Anilina/análise , Colorimetria/métodos , Substâncias Explosivas/análise , Ouro/química , Nanopartículas Metálicas/química , Nitrobenzenos/análise , Trinitrotolueno/análise , Cor , Cicloexilaminas/química , Limite de Detecção , Solo/química , Poluentes do Solo/análise , Eletricidade Estática , Tioglicolatos/química
7.
Sci Rep ; 8(1): 13554, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30202096

RESUMO

Gout is the most common arthritic disease in human but was long neglected and therapeutic options are not satisfying. However, with the recent approval of the urate transporter inhibitor lesinurad, gout treatment has experienced a major innovation. Here we show that lesinurad possesses considerable modulatory potency on peroxisome proliferator-activated receptor γ (PPARγ). Since gout has a strong association with metabolic diseases such as type 2 diabetes, this side-activity appears as very valuable contributing factor to the clinical efficacy profile of lesinurad. Importantly, despite robustly activating PPARγ in vitro, lesinurad lacked adipogenic activity, which seems due to differential coactivator recruitment and is characterized as selective PPARγ modulator (sPPARγM).


Assuntos
Gota/tratamento farmacológico , PPAR gama/agonistas , Tioglicolatos/farmacologia , Triazóis/farmacologia , Uricosúricos/farmacologia , Células 3T3 , Adipócitos/efeitos dos fármacos , Adipócitos/fisiologia , Adipogenia/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Células HEK293 , Células Hep G2 , Humanos , Camundongos , Simulação de Acoplamento Molecular , PPAR gama/química , PPAR gama/genética , PPAR gama/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Tioglicolatos/química , Tioglicolatos/uso terapêutico , Transfecção , Triazóis/química , Triazóis/uso terapêutico , Uricosúricos/uso terapêutico
8.
Ecotoxicol Environ Saf ; 163: 408-416, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30071461

RESUMO

2,2'-Thiodiacetic acid derivatives have a wide application potential, mainly in coordination chemistry. This research indicates that quaternary ammonium 2,2'-thiodiacetate salts may also be potent herbicidal agents used in agriculture. To provide a rationale for this statement, the toxic effect by a alkyl and aryl quaternary ammonium salts (QASs) on plant growth was investigated. The phytotoxicity of these compounds was tested against cultivated monocotyledonous (spring barley) and dicotyledonous (common radish) plants, whereas herbicidal activity was investigated in relation to popular weeds species (white goosefoot, sorrel and gallant-soldier). The results showed that aliphatic QASs possessed a low phytotoxicity to food crops and that some of them (in particular triethylammonium salt) had potent and selective herbicidal properties against common weeds, such as sorrel and gallant-soldier. However, the investigated compounds appeared to be ineffective herbicides against white goosefoot.


Assuntos
Herbicidas/toxicidade , Plantas Daninhas/efeitos dos fármacos , Compostos de Amônio Quaternário/toxicidade , Tioglicolatos/toxicidade , Compostos de Amônio , Asteraceae/efeitos dos fármacos , Chenopodium album/efeitos dos fármacos , Herbicidas/química , Hordeum/efeitos dos fármacos , Hordeum/crescimento & desenvolvimento , Compostos de Amônio Quaternário/química , Raphanus/efeitos dos fármacos , Raphanus/crescimento & desenvolvimento , Tioglicolatos/química , Testes de Toxicidade
9.
Biomacromolecules ; 19(9): 3766-3775, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30102855

RESUMO

In this study, native chemical ligation (NCL) was used as a selective cross-linking method to form core-cross-linked thermosensitive polymeric micelles for drug delivery applications. To this end, two complementary ABA triblock copolymers having polyethylene glycol (PEG) as midblock were synthesized by atom transfer radical polymerization (ATRP). The thermosensitive poly isopropylacrylamide (PNIPAM) outer blocks of the polymers were copolymerized with either N-(2-hydroxypropyl)methacrylamide-cysteine (HPMA-Cys), P(NIPAM- co-HPMA-Cys)-PEG-P(NIPAM- co-HPMA-Cys) (PNC) or N-(2-hydroxypropyl)methacrylamide-ethylthioglycolate succinic acid (HPMA-ETSA), P(NIPAM- co-HPMA-ETSA)-PEG-P(NIPAM- co-HPMA-ETSA) (PNE). Mixing of these polymers in aqueous solution followed by heating to 50 °C resulted in the formation of thermosensitive flower-like micelles. Subsequently, native chemical ligation in the core of micelles resulted in stabilization of the micelles with a Z-average of 65 nm at body temperature. Decreasing the temperature to 10 °C only affected the size of the micelles (increased to 90 nm) but hardly affected the polydispersity index (PDI) and aggregation number ( Nagg) confirming covalent stabilization of the micelles by NCL. CryoTEM images showed micelles with an uniform spherical shape and dark patches close to the corona of micelles were observed in the tomographic view. The dark patches represent more dense areas in the micelles which coincide with the higher content of HPMA-Cys/ETSA close to the PEG chain revealed by the polymerization kinetics study. Notably, this cross-linking method provides the possibility for conjugation of functional molecules either by using the thiol moieties still present after NCL or by simply adjusting the molar ratio between the polymers (resulting in excess cysteine or thioester moieties) during micelle formation. Furthermore, in vitro cell experiments demonstrated that fluorescently labeled micelles were successfully taken up by HeLa cells while cell viability remained high even at high micelle concentrations. These results demonstrate the potential of these micelles for drug delivery applications.


Assuntos
Reagentes para Ligações Cruzadas/química , Portadores de Fármacos/síntese química , Micelas , Resinas Acrílicas/química , Células HeLa , Humanos , Metacrilatos/química , Polietilenoglicóis/química , Coroa de Proteína/química , Temperatura Ambiente , Tioglicolatos/química
10.
J Biochem Mol Toxicol ; 32(9): e22194, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29984869

RESUMO

Carbonic anhydrase (CA) is an important metabolic enzyme family closely related to many physiological and pathological processes. Currently, carbonic anhydrase inhibitors are the target molecules in the treatment and diagnosis of many diseases. In present study, we investigated the inhibitory effects of some indazole molecules on the CA-I and CA-II isoenzymes isolated from human erythrocytes. We showed that human CA-I and CA-II activities were reduced by of some indazoles at low concentrations. IC50 values, Ki constants, and inhibition types for each indazole molecule were determined. The indazoles showed Ki constants in a range of 0.383 ± 0.021 to 2.317 ± 0.644 mM, 0.409 ± 0.083 to 3.030 ± 0.711 mM against CA-I and CA-II, respectively. Each indazole molecule exhibited a noncompetitive inhibition effect. Bromine- and chlorine-bonded indazoles were found to be more potent inhibitory effects on carbonic anhydrase isoenzymes. In conclusion, we conclude that these results may be useful in the synthesis of carbonic anhydrase inhibitors.


Assuntos
Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica I/antagonistas & inibidores , Inibidores da Anidrase Carbônica/farmacologia , Eritrócitos/enzimologia , Indazóis/farmacologia , Acetofenonas/química , Acetofenonas/farmacologia , Acetilcolinesterase/química , Acetilcolinesterase/metabolismo , Animais , Butirilcolinesterase/química , Butirilcolinesterase/metabolismo , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Anidrase Carbônica I/química , Anidrase Carbônica I/isolamento & purificação , Anidrase Carbônica I/metabolismo , Anidrase Carbônica II/isolamento & purificação , Anidrase Carbônica II/metabolismo , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Cromatografia de Afinidade , Desenho de Drogas , Electrophorus , Cavalos , Humanos , Indazóis/síntese química , Indazóis/química , Cinética , Estrutura Molecular , Nootrópicos/síntese química , Nootrópicos/química , Nootrópicos/farmacologia , Espectroscopia de Prótons por Ressonância Magnética , Tioglicolatos/química , Tioglicolatos/farmacologia
11.
Comput Biol Chem ; 76: 191-201, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30053700

RESUMO

Bacterial type II secretion system has now become an attractive target for antivirulence drug development. The aim of the present study was to characterize the binding site of the type II secretion system traffic ATPase GspER of Pseudomonas aeruginosa, and identify potent inhibitors using extensive computational and virtual screening approaches. Initially, the designed platform focused on the evolutionary relationship of ATPase GspER of P. aeruginosa, followed by protein-protein interaction network analysis to characterize its function. In addition, homology modeling, virtual screening and molecular dynamics simulation have been performed to identify potent hits and understand the ligand binding properties of ATPase GspER. According to the evolutionary relationship, high level of genetic change was observed for P. aeruginosa, bearing orthology relationships with P.alcaligenes and P.otitidis. Concurrently, the binding site analysis represented residue Gly268, Ser267, Thr270, Thr271and Lys269 in Walker A motif directly formed hydrogen bonds with the ATP, which modulates the function of ATPase GspER in the secretion process, is also validated by the molecular docking analysis and molecular dynamics simulation. Furthermore, ZINC04325133 is one of the most potent hits has been identified from virtual screening approach followed by molecular dynamics simulation and MM-GBSA binding energy analysis. These results may provide new knowledge for the development of novel therapeutic strategies against P. aeruginosa, as well as inhibiting secretion system process of a wide range of gram-negative bacteria.


Assuntos
Adenosina Trifosfatases/antagonistas & inibidores , Adenosina Trifosfatases/metabolismo , Proteínas de Bactérias/antagonistas & inibidores , Proteínas de Bactérias/metabolismo , Inibidores Enzimáticos/metabolismo , Tioglicolatos/metabolismo , Adenosina Trifosfatases/química , Antibacterianos/química , Antibacterianos/metabolismo , Proteínas de Bactérias/química , Domínio Catalítico , Inibidores Enzimáticos/química , Ligações de Hidrogênio , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Pseudomonas aeruginosa/enzimologia , Termodinâmica , Tioglicolatos/química , Sistemas de Secreção Tipo II/metabolismo
12.
Biomacromolecules ; 19(8): 3257-3267, 2018 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-29979877

RESUMO

Development of folate (FA)-functionalized gold nanoparticles (AuNPs) has greatly increased in recent years due to their potential in cancer treatment. As surface functionalization of polymer-free AuNPs with thiol groups could result in agglomeration and precipitation, AuNPs should be stabilized with an efficient polymer. In this study, citric acid-PEG branched polymer (CPEG) acted as a reducing as well as stabilizing agent in the synthesis of AuNPs. The thiol group of thioglycolic acid (TGA) attached to CPEG-stabilized AuNPs and interacted with the free carboxylic acid group on the surface of TGA-AuNP nanoconjugates. Stable TGA-AuNP nanoconjugates were obtained only with CPEG-stabilized AuNPs and not with citrate-stabilized AuNPs. The carboxylic acid group on the surface of AuNPs was used to attach FA via an EDC/NHS coupling reaction to obtain FA-TGA-AuNP nanoconjugates. In vitro cytotoxicity studies indicated that FA-TGA-AuNPs were not toxic to normal cells up to a concentration of 200 µg/mL. However, FA-TGA-AuNP nanoconjugates effectively inhibited proliferation of MCF-7 cancer cells at a low concentration of 25 µg/mL after 3 days of incubation. The anticancer activity of FA-TGA-AuNPs was enhanced by incorporating the anticancer drug 5-fluorouracil into the nanoconjugates, which exhibited sustained drug release up to 5 days. Hence, the developed biocompatible FA-TGA-AuNPs could be used for specific killing of breast cancer cells.


Assuntos
Antineoplásicos/química , Ácido Fólico/análogos & derivados , Ouro/química , Nanopartículas Metálicas/química , Tioglicolatos/química , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Ácido Cítrico/análogos & derivados , Fluoruracila/química , Fluoruracila/farmacologia , Humanos , Células MCF-7 , Polietilenoglicóis/química
13.
Cell Mol Biol (Noisy-le-grand) ; 64(7): 1-7, 2018 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-29974838

RESUMO

Reviewing the mode of interaction between this kind of active pharmaceutical ingredients and DNA has received much more attention in current years. Anthracycline drugs such as Epirubicin are frequently used in cancer treatment for breast cancer treatment. In the present study, the Epirubicin -calf thymus DNA interaction was investigated by using spectroscopic, fluorimetric and molecular docking methods. Water-soluble quantum dots (QDs) with nanometric particle size fabricated and characterized by transmission electron microscope and photon correlation spectroscopy. The binding constant value and the free energy change for this interaction were obtained to be 3.00×106 M-1 and -42.26 kJ mol-1, using the spectroscopic method and docking investigations, respectively. Additionally, fluorescent thioglycolic acid-capped CdTe QDs were used for investigation of EPI and DNA interaction. Epirubicin as a quencher quenched the fluorescence of CdTe QDs after electrostatic adsorption on the surface of QDs. With the addition of DNA, EPI will be desorbed from the surface of CdTe QDs, inserted into the DNA. Subsequently, fluorescence changes of QDs were used for calculation of binding constant value, which was in good agreement with that obtained by the spectroscopic method. By the comparison of the achieved results, the intercalation mode of interaction between Epirubicin and DNA proved.


Assuntos
Antibióticos Antineoplásicos/química , DNA/química , Epirubicina/química , Simulação de Acoplamento Molecular , Pontos Quânticos/química , Espectrofotometria Ultravioleta , Cloreto de Cádmio/química , Fluorescência , Interações Hidrofóbicas e Hidrofílicas , Conformação Molecular , Nanopartículas/química , Tamanho da Partícula , Telúrio/química , Tioglicolatos/química
14.
J Pharm Biomed Anal ; 158: 236-246, 2018 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-29886371

RESUMO

Potentiometric and spectrophotometric pH-titrations of the lesinurad for three consecutive dissociation constants determination were compared. Lesinurad is a selective inhibitor of uric acid reabsorption as part of a combination of medicines to treat high levels of uric acid in blood, also called hyperuricemia. Nonlinear regression of the pH-spectra with REACTLAB and SQUAD84 and of the pH-titration curve with ESAB determined three multiple close dissociation constants. The protonation scheme of lesinurad was suggested. A sparingly soluble anion L- of lesinurad was protonated to the still soluble species LH, LH2+ and LH32+ in pure water. Three consecutive thermodynamic dissociation constants were estimated pKTa1 = 2.09, pKTa2 = 4.25, pKTa3 = 6.58 at 25 °C and pKTa1 = 1.96, pKTa2 = 4.16, pKTa3 = 6.32 at 37 °C by UV-metric spectra analysis. The graph of molar absorption coefficients shows that the spectrum of species LH2+ and LH vary in colour, while protonation of chromophore LH2+ to LH32+ has less influence on chromophores in the lesinurad molecule. Three multiple thermodynamic dissociation constants of 1 × 10-4 M lesinurad were determined by the pH-metric analysis pKTa1 = 2.39, pKTa2 = 3.47, pKTa3 = 6.17 at 25 °C and pKTa1 = 2.08, pKTa2 = 3.29, pKTa3 = 6.03 at 37 °C. The values of enthalpy ΔH0(pKa1) = 19.19 kJ mol-1, ΔH0(pKa2) = 13.29 kJ mol-1, ΔH0(pKa3) = 38.39 kJ mol-1, show the dissociation process is endothermic. The positive values of ΔG0(pKa1) = 11.93 kJ mol-1, ΔG0(pKa2) = 24.26 kJ mol-1, ΔG0(pKa3) = 37.56 kJ mol-1 at 25 °C indicate that the dissociation process of pKa2 is not spontaneous, which was confirmed by its value of entropy ΔS0(pKa1) = 24.37 J mol-1, ΔS0(pKa2) = -36.79 J mol-1, ΔS0(pKa3) = 2.79 J mol-1. Three macro-dissociation constants of lesinurad and protonation locations were predicted by MARVIN and ACD/Percepta.


Assuntos
Potenciometria/métodos , Espectrofotometria Ultravioleta/métodos , Termodinâmica , Tioglicolatos/química , Triazóis/química , Uricosúricos/química , Química Farmacêutica , Concentração de Íons de Hidrogênio , Potenciometria/instrumentação , Espectrofotometria Ultravioleta/instrumentação
15.
Biomacromolecules ; 19(6): 2109-2116, 2018 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-29664626

RESUMO

Stimuli-responsive polymers have received increasing interest for a variety of applications. Here, we report a series of unique charge-determined thermoresponsive polypeptoids synthesized by a combination of ring-opening polymerization and click chemistry. The LCST-type and UCST-type behavior is mainly dominated by the charge state on the side chain. Further, the phase transition temperature highly depends on the degree of polymerization, the side-chain architecture, the pH value, and so on. The obtained polypeptoid solutions exhibit good stability against temperature and salt concentration. To our knowledge, this report presents the first charge-determined LCST/UCST-type polymer from identical homopolymer backbone that displays a wide range of tunable cloudy points in aqueous media. We propose the hydrogen-bonding interaction plays a critical part on the solution behavior. These features make polypeptoids ideal candidates for highly designable stimuli-responsive polymeric materials.


Assuntos
Peptídeos/química , Polímeros/química , Química Click , Ligações de Hidrogênio , Concentração de Íons de Hidrogênio , Espectroscopia de Ressonância Magnética , Transição de Fase , Polimerização , Soluções/química , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura Ambiente , Tioglicolatos/química
16.
Food Chem ; 259: 245-250, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29680050

RESUMO

A highly selective colorimetric detection method for putrescine on the basis of an optimized derivatization reaction was established. With the aids of o-phthalaldehyde (OPA) and thioglycolic acid (TGA), putrescine was derived to become red derivatives (PUT-RD), the form that can be detected qualitatively and quantitatively by visual inspection and UV-vis spectrophotometer at λmax of 490 nm, respectively. Key parameters affecting the experiment were investigated by one-factor-at-a-time and response surface analysis. At the optimal condition, this colorimetric method achieved good linearity at putrescine concentrations ranging from 0.8 to 200 µM with detection limit of 0.44 µM. The method also has good selectivity when common amino acids and inorganic ions, as well as ethylenediamine, 1,3-propanediamine, 1,5-pentanediamine, and 1,6-hexanediamine were used as interferences. The established colorimetric method was successfully employed for the detection of putrescine in 10 commercial fish products.


Assuntos
Produtos Pesqueiros/análise , Putrescina/análise , Espectrofotometria , o-Ftalaldeído/química , Aminoácidos/química , Animais , Concentração de Íons de Hidrogênio , Limite de Detecção , Concentração Osmolar , Temperatura Ambiente , Tioglicolatos/química
17.
Artigo em Inglês | MEDLINE | ID: mdl-29428898

RESUMO

A fluorescent sensor based on thioglycolic acid-capped cadmium sulfide quantum dots (TGA-CdS QDs) has been designed for the sensitive and selective detection of dopamine (DA). In the presence of dopamine (DA), the addition of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS) activates the reaction between the carboxylic group of the TGA and the amino group of dopamine to form an amide bond, quenching the fluorescence of the QDs. The fluorescence intensity of TGA-CdS QDs can be used to sense the presence of dopamine with a limit of detection of 0.68µM and a working linear range of 1.0-17.5µM. This sensor system shows great potential application for dopamine detection in dopamine drug samples and for future easy-to-make analytical devices.


Assuntos
Compostos de Cádmio/química , Dopamina/análise , Neurotransmissores/análise , Pontos Quânticos , Espectrometria de Fluorescência/métodos , Sulfetos/química , Tioglicolatos/química , Etildimetilaminopropil Carbodi-Imida/química , Limite de Detecção , Modelos Lineares , Nanopartículas Metálicas/química , Reprodutibilidade dos Testes , Succinimidas/química
18.
J Chromatogr Sci ; 56(4): 358-366, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29474515

RESUMO

Lesinurad is a novel selective uric acid reabsorption inhibitor which has been newly approved for the treatment of the chronic gout. The behavior of lesinurad under various stress conditions (hydrolysis, oxidation, thermal and photolysis) has been investigated as per ICH guidelines. The drug has been found to be labile to acidic hydrolysis, basic hydrolysis and oxidation but stable in neutral, thermal and photolytic conditions. A high performance liquid chromatographic method has been developed for selective determination of the studied drug in the presence of its related degradation products. Good chromatographic resolution has been achieved using a reversed phase BDS Hypersil C18 stationary phase with an isocratic elution of a mobile phase consists of acetonitrile:water (65:35, v/v) at a flow rate of 1 mL/min and UV detection at 290 nm. Two degradation products have been identified by IR and mass spectral scans. The method was validated according to ICH guidelines. The linearity range has been found to be acceptable over the concentration range of 1-20 µg/mL. The developed method has been successfully applied for the estimation of lesinurad in its pharmaceutical dosage form and could be used for the routine analysis of the studied drug in the quality control laboratories.


Assuntos
Tioglicolatos/análise , Tioglicolatos/química , Triazóis/análise , Triazóis/química , Acetonitrilos , Cromatografia Líquida de Alta Pressão/métodos , Estabilidade de Medicamentos , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes
19.
Artigo em Inglês | MEDLINE | ID: mdl-29126005

RESUMO

A simple and selective colorimetric sensor thioglycolic acid capped silver nanoparticles (TGA-AgNPs) was developed for the detection of 6-benzylaminopurine (6-BAP). The synthesized TGA-AgNPs were characterized by UV-vis spectroscopy, dynamic light scattering (DLS), and transmission electron microscopic (TEM) techniques. The TGA-AgNPs as a sensor for binding 6-BAP through hydrogen-bonding and π-π bonding that causes large conjugate clusters, resulting in a color change from yellow to reddish orange. The surface plasmon resonance (SPR) band of TGA-AgNPs at 397nm is red-shifted to 510nm, which confirms that 6-BAP induces the aggregation of TGA-AgNPs. Under the optimized conditions, a linear relationship between the absorption ratio (A510nm/A397nm) and 6-BAP concentration was found in the range of 4-26µM. The detection limit of 6-BAP was 0.2µM, which is lower than the other analytical techniques. Moreover, the proposed sensor was successfully applied for the detection of 6-BAP in environmental samples with good recoveries. The proposed assay provides a simple and cost-effective method for the analysis of 6-BAP in vegetable and water samples.


Assuntos
Compostos de Benzil/química , Colorimetria/métodos , Meio Ambiente , Nanopartículas Metálicas/química , Purinas/química , Prata/química , Tioglicolatos/química , Tampões (Química) , Concentração de Íons de Hidrogênio , Conformação Molecular , Soluções , Soja/química , Espectrofotometria Ultravioleta , Água/química
20.
Int J Pharm ; 537(1-2): 245-256, 2018 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-29288808

RESUMO

Low aqueous solubility and intestinal permeability limit the oral chemotherapy efficacy of paclitaxel (PTX). Traditional nanodrug delivery systems show excellent aqueous solubility improved ability of PTX. However, gastrointestinal (GI) mucus limits the improvement of intestinal permeability in traditional nanodrug delivery systems. A novel mucus adhesion- and penetration-functionalized chitosan-thioglycolic acid-Pluronic F127 (CS-TGA-PF) liposome system was developed for PTX oral delivery. The optimized formulation of PTX-loaded CS-TGA-PF liposomes showed particle size of 121.4 nm and zeta potential of 50.2 mV. CS-TGA-PF liposomes were more stable than unmodified liposomes and demonstrated a sustained-release manner of PTX incubated in simulated gastric fluid and intestinal fluid. CS-TGA-PF liposomes absorbed a three-fold amount of mucin compared with that of unmodified liposomes, which would prolong the residence time of liposomes on the mucosal surface in the intestinal tract. The intestinal mucus adhesion- and penetration-enhanced efficacy of CS-TGA-PF liposomes for intestinal PTX delivery was studied by observing the intestinal absorption and distribution. Results exhibited increased liposome uptake by the GI mucosa and improved drug intestinal absorption. In conclusion, the dual functional CS-TGA-PF liposomes with mucus adhesion- and permeation-enhanced properties could be used as a promising nanodrug delivery system for PTX oral delivery.


Assuntos
Lipossomos/química , Paclitaxel/química , Administração Oral , Animais , Quitosana/análogos & derivados , Quitosana/química , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Sistemas de Liberação de Medicamentos/métodos , Trato Gastrointestinal/metabolismo , Absorção Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Tamanho da Partícula , Permeabilidade/efeitos dos fármacos , Poloxâmero/química , Solubilidade/efeitos dos fármacos , Suínos , Tioglicolatos/química
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