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1.
J Sci Food Agric ; 100(1): 315-324, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31525262

RESUMO

BACKGROUND: In order to utilize tilapia skin gelatin hydrolysate protein, which is normally discarded as industrial waste in the process of fish manufacture, we study the in vivo and in vitro angiotensin-I-converting enzyme (ACE) inhibitory activity of the peptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP). The aim was to provide a pharmacological basis of the development of minimal side effects of ACE inhibitors by comparative analysis with captopril in molecular docking. RESULTS: This peptide from protein-rich wastes showed excellent ACE inhibitory activity (IC50  = 2.577 µmol L-1 ) and exhibited a mixed noncompetitive inhibitory pattern with Lineweaver-Burk plots. Furthermore, LSGYGP and captopril groups both showed significant decreases in blood pressure after 6 h and maintained good digestive stability over 4 h. Molecular bond interactions differentiate competitive captopril upon hydrogen bond interactions and Zn(II) interaction. The C-terminal Pro generates three interactions (hydrogen bonds, hydrophilic interactions and Van der Waals interactions) in the peptide and effectively interacts with the S1 and S2 pockets of ACE. CONCLUSION: LSGYGP, with an IC50 value of 2.577 µmol L-1 , has an antihypertensive effect in spontaneously hypertensive rats. Through comparison with captopril, this study revealed that LSGYGP may be a potential food-derived ACE inhibitory peptide and could act as a functional food ingredient to prevent hypertension. © 2019 Society of Chemical Industry.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Anti-Hipertensivos/química , Captopril/química , Hipertensão/tratamento farmacológico , Peptídeos/química , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Captopril/administração & dosagem , Ciclídeos , Digestão , Proteínas de Peixes/química , Trato Gastrointestinal/metabolismo , Humanos , Ligações de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Cinética , Masculino , Simulação de Acoplamento Molecular , Peptídeos/metabolismo , Peptídeos/farmacologia , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Hidrolisados de Proteína/química , Hidrolisados de Proteína/metabolismo , Ratos , Ratos Endogâmicos SHR
2.
Recent Pat Biotechnol ; 13(3): 239-248, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30747089

RESUMO

BACKGROUND: Hypertension is the chronic medical condition and it affected billions of people worldwide. Natural medicines are the main alternatives to treatment for a majority of people suffering from hypertension. Niazicin-A, Niazimin-A, and Niaziminin-B compounds from Moringa oleifera ethanolic leave extract were reported to have potent antihypertensive activity. OBJECTIVE: These compounds were targeted with Angiotensin-converting enzyme [ACE] which is one of the main regulatory enzymes of the renin-angiotensin system. METHODS: Protein-ligand docking of these compounds with [ACE] [both domain N and C] was conceded out through Autodock vina and visualization was done by chimera. Pharmacokinetics study of these compounds was predicted by ADME-Toxicity Prediction. RESULTS: Niazicin-A, Niazimin-A, and Niaziminin-B showed high binding affinity with ACE and partially blocked the active sites of the enzyme. Niazicin-A, Niazimin-A and Niaziminin-B showed the estimated free binding energy of -7.6kcal/mol kcal/mol, -8.8kcal/mol and -8.0kcal/mol respectively with C-domain of ACE and -7.9kcal/mol, -8.5kcal/mol and -7.7kcal/mol respectively with N-domain of ACE. The compounds showed better binding energy with angiotensinconverting enzyme in comparison to Captopril -5.5kcal/mol and -5.6kcal/mol and Enalapril [standard] -8.4kcal/mol and -7.5kcal/mol with C and N domain, respectively. CONCLUSION: Computationally, the selected bioactive molecules have shown better binding energy to known standard drugs which have been already known for inhibition of ACE and can further act as a pharmacophore for in vitro and in vivo studies in the development of alternative medicine.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Anti-Hipertensivos/química , Moringa oleifera/química , Peptidil Dipeptidase A/química , Tiocarbamatos/química , Inibidores da Enzima Conversora de Angiotensina/isolamento & purificação , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Anti-Hipertensivos/isolamento & purificação , Anti-Hipertensivos/metabolismo , Captopril/química , Captopril/metabolismo , Domínio Catalítico , Enalapril/química , Enalapril/metabolismo , Expressão Gênica , Humanos , Hipertensão/tratamento farmacológico , Hipertensão/enzimologia , Cinética , Simulação de Acoplamento Molecular , Patentes como Assunto , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Extratos Vegetais/química , Folhas de Planta/química , Ligação Proteica , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Domínios e Motivos de Interação entre Proteínas , Especificidade por Substrato , Termodinâmica , Tiocarbamatos/isolamento & purificação , Tiocarbamatos/metabolismo
3.
Eur J Pharm Sci ; 132: 163-173, 2019 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-30695689

RESUMO

The present study aimed to investigate the potential of zein (a protein obtained from corn) for development of gastroretentive floating tablets for the first time. A compression coated tablet design with outer floating layer and inner drug containing layer was followed to achieve floating over gastric fluid with sustained release of drug. Captopril was used as a model drug for this purpose. Eight formulations were developed and the influence of different components on drug release and floating behavior was evaluated. The drug in coating layer was found to be released at faster rate while sustained release behavior was observed from core layer. In vivo pharmacokinetic studies on rabbits showed significant increase in bioavailability and mean residence time (MRT). Moreover, radiographic study exhibited gastric retention of prepared tablets >12 h. In conclusion, zein can be used for development of gastroretentive floating tablets and by adjusting amount of different formulation factors, desired drug release rate can be achieved.


Assuntos
Captopril/química , Captopril/farmacocinética , Desenho de Drogas , Mucosa Gástrica/metabolismo , Zeína/química , Administração Oral , Animais , Disponibilidade Biológica , Captopril/administração & dosagem , Liberação Controlada de Fármacos , Feminino , Absorção Gástrica , Coelhos , Solubilidade , Propriedades de Superfície , Comprimidos
4.
Mater Sci Eng C Mater Biol Appl ; 94: 879-885, 2019 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-30423775

RESUMO

In the present study, electrochemical studies and potentiometric determination of captopril (CAP) drug were presented using a glassy carbon electrode (GCE) and carbon paste electrode (CPE), respectively; which is modified with a synthetic nano-structured molecularly imprinted polymer (MIP). CAP-MIP sample with an average particle size of 95 nm was synthesized using a precipitation polymerization method. The electrochemical behavior of CAP was studied on a MIP modified GCE, in an aqueous solution at pH 3.0. The electron transfer coefficient (α) was determined for the CAP drug, using electrochemical approaches. The prepared CAP-MIP was also used as a modifier in a CPE to design a selective CAP sensor, before its potentiometric determination. The modified CPE exhibits a good electrochemical response with a Nernstian slope of 59.15 ±â€¯1.5 mV per decade over a wide linearity in the concentration range of 3.0 × 10-9-1.0 × 10-1 mol L-1. The cyclic voltammetry results were in good agreement with the electrochemical studies for the 1H+/1e- process. The designed electrode indicates a reasonable selectivity for CAP over other studied drugs such as ibuprofen, paracetamol, acyclovir, pyrazinamide, dimenhydrinate, and naproxen as well as with an excellent applicability in some pharmaceutical products.


Assuntos
Captopril/análise , Técnicas Eletroquímicas/instrumentação , Impressão Molecular , Nanoestruturas/química , Polímeros/química , Captopril/química , Carbono/química , Eletrodos , Vidro/química , Concentração de Íons de Hidrogênio , Reprodutibilidade dos Testes , Espectroscopia de Infravermelho com Transformada de Fourier , Comprimidos , Fatores de Tempo
5.
Free Radic Biol Med ; 129: 107-115, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30227269

RESUMO

S-nitrosocaptopril (CapNO) possesses dual capacities of both Captopril and an NO donor with enhanced efficacy and reduced side effects. CapNO crystals are difficult to make due to its unstable S-NO bond. Here, we report a novel stable S-nitrosocaptopril monohydrate (CapNO·H2O) that is stabilized by intermolecular five-membered structure, where one H of H2O forms a hydrogen bond with O- of the stable resonance zwitterion Cap-S+=N-O-, and the O in H2O forms the dipole-dipole interaction with S+ through two unpaired electrons. With the chelation and common ion effect, we synthesized and characterized CapNO·H2O that is stable at 4 °C for 180 days and thereafter without significant degradation. Compared to Captopril, CapNO showed direct vasorelaxation and beneficial effect on PAH rats, and could be self-assembled in rat stomach when Captopril and NaNO2 were given separately. This novel CapNO·H2O with low entropy paves an avenue for its clinical trials and commercialization.


Assuntos
Anti-Hipertensivos/farmacologia , Captopril/análogos & derivados , Hipertensão Pulmonar/tratamento farmacológico , Doadores de Óxido Nítrico/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Anti-Hipertensivos/síntese química , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta/fisiopatologia , Captopril/administração & dosagem , Captopril/síntese química , Captopril/química , Captopril/metabolismo , Captopril/farmacologia , Cristalização , Modelos Animais de Doenças , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/metabolismo , Ventrículos do Coração/fisiopatologia , Humanos , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/fisiopatologia , Masculino , Doadores de Óxido Nítrico/síntese química , Ratos , Ratos Sprague-Dawley , Nitrito de Sódio/administração & dosagem , Nitrito de Sódio/química , Nitrito de Sódio/metabolismo , Estômago/química , Técnicas de Cultura de Tecidos , Resistência Vascular/efeitos dos fármacos , Vasodilatação/fisiologia , Vasodilatadores/síntese química
6.
Biol Pharm Bull ; 41(12): 1837-1842, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30259884

RESUMO

We show that a lectin like protein from the mushroom Agaricus bisporus (LSMT) is capable to permeate the epithelial monolayer barrier of the intestine ex vivo. The protein is not toxic or immunogenic upon prolonged administration and elevated dose in mice. Thus, it could be a candidate as a drug carrier for oral administration. However, its permeability should be tested after the protein has been modified, mimicking the condition in which it is used as a drug carrier. The protein was conjugated to captopril, the selected model of a Biopharmaceutical Classification System (BCS) class III drug, with high solubility but poor permeability. The drug was conjugated to LSMT that had been modified with 4-succinimidyloxycarbonyl-alpha-methyl-2-pyridyldithiotoluene (SMPT) as a linker. The success of LSMT modification was confirmed with TLC and MS; the latter also indicated the amount of captopril molecule linked. The modified LSMT could permeate through the intestinal monolayer barrier, and thus could be absorbed in the intestine after modification. The modified protein appears to remain stable after incubation in simulated gastrointestinal fluids. This pioneering work provides an essential basis for further development of the protein as a drug carrier for oral administration.


Assuntos
Agaricus , Captopril/química , Portadores de Fármacos/química , Monofenol Mono-Oxigenase/química , Administração Oral , Agaricales/metabolismo , Agaricus/metabolismo , Células CACO-2 , Captopril/administração & dosagem , Captopril/metabolismo , Portadores de Fármacos/administração & dosagem , Portadores de Fármacos/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Ácido Gástrico/metabolismo , Humanos , Absorção Intestinal/efeitos dos fármacos , Absorção Intestinal/fisiologia , Monofenol Mono-Oxigenase/administração & dosagem , Monofenol Mono-Oxigenase/metabolismo
7.
Anal Bioanal Chem ; 410(28): 7373-7384, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30191274

RESUMO

Here, one kind of hydrophilic hydroxypropyl ß-cyclodextrin cross-linked polymer (HP-CDP) was prepared and used to establish a "turn-on" fluorescent probe for selective determination of captopril in biological samples. The HP-CDP has been synthesized in one step by cross-linking (2-hydroxypropyl)-ß-cyclodextrin (HP-ß-CD) with a rigid aromatic group linker tetrafluoroterephthalonitrile (TFT), and the synthesis parameters of HP-CDP were optimized with water solubility, yield, and adsorption capacity as indicators. When it was used as a luminescent material, we have found an interesting phenomenon that the fluorescence emission of HP-CDP was quenched after forming a coordination compound with ferric ions, and then recovered after adding a certain concentration of captopril, since captopril can reduce the ferric iron to ferrous ions and cause ligand replacement. Based on this observation, a novel turn-on fluorescent method was developed for the determination of captopril. The method exhibited good linearity in the range of 9.2 × 10-7 to 4.6 × 10-4 M (R2 = 0.9982) and a low detection limit of 1.8 × 10-7 M at optimum HP-CDP concentration, ferric ion concentration, pH, and incubation time. Moreover, interference experiments demonstrated that this fluorescence sensor had excellent selectivity that can commendably resist the interference from potential foreign substances. The proposed method has been successfully applied to determine captopril in human urine samples and may provide outstanding application potential in the future development of sensors. In addition, it is believed that HP-CDP also has a wide range of applications, for example, as a solubilizer, pollutant adsorbent, or drug carrier. Graphical abstract ᅟ.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Captopril/urina , Captopril/química , Corantes Fluorescentes , Humanos , Concentração de Íons de Hidrogênio , Ferro , Modelos Moleculares , Estrutura Molecular , Fatores de Tempo , Água
8.
Proc Natl Acad Sci U S A ; 115(41): 10511-10516, 2018 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-30249662

RESUMO

Effective delivery of drug carriers selectively to the kidney is challenging because of their uptake by the reticuloendothelial system in the liver and spleen, which limits effective treatment of kidney diseases and results in side effects. To address this issue, we synthesized l-serine (Ser)-modified polyamidoamine dendrimer (PAMAM) as a potent renal targeting drug carrier. Approximately 82% of the dose was accumulated in the kidney at 3 h after i.v. injection of 111In-labeled Ser-PAMAM in mice, while i.v. injection of 111In-labeled unmodified PAMAM, l-threonine modified PAMAM, and l-tyrosine modified PAMAM resulted in kidney accumulations of 28%, 35%, and 31%, respectively. Single-photon emission computed tomography/computed tomography (SPECT/CT) images also indicated that 111In-labeled Ser-PAMAM specifically accumulated in the kidneys. An intrakidney distribution study showed that fluorescein isothiocyanate-labeled Ser-PAMAM accumulated predominantly in renal proximal tubules. Results of a cellular uptake study of Ser-PAMAM in LLC-PK1 cells in the presence of inhibitors [genistein, 5-(N-ethyl-N-isopropyl)amiloride, and lysozyme] revealed that caveolae-mediated endocytosis, micropinocytosis, and megalin were associated with the renal accumulation of Ser-PAMAM. The efficient renal distribution and angiotensin-converting enzyme (ACE) inhibition effect of captopril (CAP), an ACE inhibitor, was observed after i.v. injection of the Ser-PAMAM-CAP conjugate. These findings indicate that Ser-PAMAM is a promising renal targeting drug carrier for the treatment of kidney diseases. Thus, the results of this study demonstrate efficient renal targeting of a drug carrier via Ser modification.


Assuntos
Captopril/farmacologia , Dendrímeros/administração & dosagem , Portadores de Fármacos/administração & dosagem , Sistemas de Liberação de Medicamentos , Nefropatias/tratamento farmacológico , Poliaminas/química , Serina/química , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/química , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Captopril/administração & dosagem , Captopril/química , Dendrímeros/química , Portadores de Fármacos/química , Camundongos
9.
Talanta ; 189: 339-344, 2018 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-30086928

RESUMO

A simple, accurate, and low-cost analytical procedure for captopril determination through digital imaging is presented. The method relies on the spot test reaction between captopril and palladium (II) chloride, which produces a yellow and water-soluble complex with maximum absorption at 380 nm. A smartphone camera and a portable apparatus built for internal lighting control were put together to acquire digital images of reaction mixtures. Digital image processing through the RGB approach was used to establish a quantitative relationship between color intensity and captopril concentration. Under the most suitable operational and experimental conditions, an analytical curve was built monitoring the Blue channel within the concentration range of 3.12 × 10-5 to 1.21 × 10-3 mol L-1. Limits of detection and quantification were equal to 8.06 × 10-6 and 2.69 × 10-5 mol L-1, respectively. Recovery percentage in synthetic urine samples ranged from 97.1% to 102.9%. Results were compared with a reference method and no significant differences were detected at the 95% confidence level. The developed method presents budgetary and environmental advantages concerning the use of cheap and easy-handled devices and the consumption of very low volumes of reagent (800 µL per determination). It can be a useful analytical tool for laboratories with limited financial resources while abiding by green chemistry principles.


Assuntos
Materiais Biomiméticos/química , Captopril/análise , Captopril/urina , Smartphone , Urinálise/métodos , Captopril/química , Colorimetria , Custos e Análise de Custo , Formas de Dosagem , Modelos Moleculares , Conformação Molecular
10.
Mikrochim Acta ; 185(9): 422, 2018 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-30128634

RESUMO

The authors describe the synthesis of fluorescent coral-like carbon nano-branched polymers (PCNBPs) co-doped with nitrogen and phosphorus. Uric acid and phosphoric acid act as nitrogen and phosphorus sources, respectively. The PCNBPs have a coral-like branched structure, are cross-connected, and < 20 nm in skeleton diameter. Their blue fluorescence, best measured at excitation/emission wavelengths of 330/425 nm, is quenched by mercury (II) ions due to the specifically restricted rigid conformation caused by the interaction of phosphorus, nitrogen, and oxygen groups on the surface of the PCNBPs. Fluorescence is selectivity quenched by Hg(II) but restored in addition of the hypertension drug captopril (CAP) in the range 50 nM to 40 µM concentration range. Fluorescence recovery is attributed to the effectively specific interactions between the thiol group of CAP and Hg(II). The method was applied to the determination of the concentration of Cap in pharmaceutical samples, and recoveries were between 97.6 and 105.1%. Graphical abstract Fluorescent coral-like carbon nano-branched polymers (PCNBPs) co-doped with nitrogen and phosphorus are described. Their fluorescence is selectivity quenched by Hg(II) but restored in addition of the hypertension drug captopril (Cap) in the range 50 nM to 40 µM concentration range.


Assuntos
Antozoários/química , Materiais Biomiméticos/química , Captopril/análise , Captopril/química , Carbono/química , Fluorometria/métodos , Polímeros/química , Animais , Corantes Fluorescentes/química , Luminescência , Mercúrio/química , Modelos Moleculares , Conformação Molecular , Temperatura Ambiente
11.
J Mol Graph Model ; 84: 82-89, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29936366

RESUMO

The perils of antimicrobial drug resistance can be overcome by finding novel antibiotic targets and corresponding small molecule inhibitors. Microbial enzyme DapE is a promising antibiotic target due to its importance to the bacterial survival. The potency of L-Captopril, a well known angiotensin-converting enzyme inhibitor, as an inhibitor of DapE enzyme has been evaluated by analyzing its binding modes and binding affinity towards DapE enzyme. L-Captopril is found to bind the metal centers of DapE enzyme either via its thiolate group or through its carboxylate group. While the latter binding mode is found to be thermodynamically favorable, the former binding mode, also seen in the crystal structure, is kinetically favored. To optimize the binding affinity of the inhibitor towards DapE enzyme, a series of L-Captopril-based inhibitors have been modelled by changing the side groups of L-Captopril. The introduction of a bipolar functional group at the C4 position of the pyrrolidine ring of L-Captopril and the substitution of the thiol group with a carboxylate group, have been shown to provide excellent enzyme affinity that supersedes the binding affinity of DapE enzyme towards its natural substrate, thus making this molecule a potential inhibitor with great promise.


Assuntos
Amidoidrolases/química , Captopril/análogos & derivados , Captopril/química , Inibidores Enzimáticos/química , Amidoidrolases/metabolismo , Captopril/farmacologia , Avaliação Pré-Clínica de Medicamentos , Reposicionamento de Medicamentos , Inibidores Enzimáticos/farmacologia , Modelos Moleculares , Conformação Molecular , Ligação Proteica , Relação Quantitativa Estrutura-Atividade
12.
Luminescence ; 33(5): 954-961, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29770991

RESUMO

Both the molecular recognition and interaction of metallo-ß-lactamase CcrA with l-captopril were studied by the combined use of fluorescence spectra and molecular dynamic simulation. The results showed that the binding constant was 8.89 × 104  L mol-1 at 296 K. Both Zn1 and Zn2 displayed tetrahedral coordination geometries in the CcrA-Lcap complex, the S atom in l-captopril displaced the nucleophilic hydroxide in apo CcrA and occupied the fourth coordination site for each ion, resulting in a competitively inhibited CcrA enzyme. Strong electrostatic interaction between the two zinc ions in CcrA and negatively charged l-captopril provided the main driving force for the binding affinity. Through a partly structural transformation from ß-sheet to random coil, loop 1 (residues 24-34) completely opened the binding pocket of CcrA to allow an induced fit of the newly introduced ligand. This study may provide some valuable information for designing and developing a more tightly binding inhibitor to resist superbugs.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Captopril/química , Captopril/metabolismo , beta-Lactamases/química , beta-Lactamases/metabolismo , Modelos Moleculares , Simulação de Dinâmica Molecular , Conformação Proteica , Estabilidade Proteica , Espectrometria de Fluorescência/métodos , Espectrofotometria Ultravioleta
13.
J Mol Recognit ; 31(8): e2715, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29630759

RESUMO

In the present study, the interaction of human serum albumin (HSA) with some cardiovascular drugs (CARs) under physiological conditions was investigated via the fluorescence spectroscopic and Fourier transform infrared spectroscopy. The CAR included Captopril, Timolol, Propranolol, Atenolol, and Amiodarone. Cardiovascular drugs can effectively quench the endogenous fluorescence of HSA by static quenching mechanism. The fluorescence quenching of HSA is mainly caused by complex formation of HSA with CAR. The binding reaction of CAR with HSA can be concluded that hydrophobic and electrostatic interactions are the main binding forces in the CAR-HSA system. The results showed that CAR strongly quenched the intrinsic fluorescence of HSA through a static quenching procedure, and nonradiation energy transfer happened within molecules. Fourier transform infrared spectroscopy absorption studies showed that the secondary structure was changed according to the interaction of HSA and CAR. The binding reaction of CAR with HSA can be concluded that hydrophobic and electrostatic interactions are the main binding forces in the CAR-HSA system. The results obtained herein will be of biological significance in pharmacology and clinical medicines.


Assuntos
Fármacos Cardiovasculares/química , Ligação Proteica/efeitos dos fármacos , Albumina Sérica Humana/química , Amiodarona/química , Amiodarona/farmacologia , Atenolol/química , Atenolol/farmacologia , Captopril/química , Captopril/farmacologia , Fármacos Cardiovasculares/uso terapêutico , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Propranolol/química , Propranolol/farmacologia , Albumina Sérica Humana/efeitos dos fármacos , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Timolol/química , Timolol/farmacologia
14.
J Agric Food Chem ; 66(14): 3700-3707, 2018 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-29569905

RESUMO

Grape seed extract contains a high content of proanthocyanidins that can be depolymerized into C-4-substituted (epi)catechin derivatives in the presence of nucleophiles. However, the biological and medicinal values of depolymerization products have been rarely investigated. Recently, we developed a novel depolymerization product (-)-epicatechin-4ß- S-captopril methyl ester (ECC) derived from the reaction of grape seed proanthocyanidin extract with captopril in the presence of acidified methanol. A central composite design was employed to select the most appropriate depolymerization temperature and time to obtain the target product ECC with a high yield. A total of 16 metabolites of ECC in rat urine, feces, and plasma were identified using liquid chromatography quadrupole time-of-flight tandem mass spectrometry. The in vivo results suggested that ECC could release captopril methyl ester and epicatechin, followed by the generation of further metabolites captopril and epicatechin sulfate conjugates. Therefore, ECC may be used as a potential prodrug with synergistic or additive hypotensive effects.


Assuntos
Anti-Hipertensivos/síntese química , Anti-Hipertensivos/metabolismo , Extrato de Sementes de Uva/química , Extrato de Sementes de Uva/metabolismo , Hipertensão/tratamento farmacológico , Proantocianidinas/química , Proantocianidinas/metabolismo , Pró-Fármacos/síntese química , Pró-Fármacos/metabolismo , Vitis/química , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/química , Captopril/química , Extrato de Sementes de Uva/administração & dosagem , Humanos , Hipertensão/metabolismo , Masculino , Polimerização , Proantocianidinas/administração & dosagem , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , Ratos , Ratos Sprague-Dawley , Sementes/química , Urina/química
15.
Sci Rep ; 7(1): 8867, 2017 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-28827527

RESUMO

Hypertension has been recognized as one of the highest risk factors for cardiovascular diseases. Anti-hypertension agent screening and development has been recognized as a pharmaceutical therapy approach for the cardiovascular diseases treatment. Many kinds of traditional Chinese medicines, such as pine needle, have been used for the treatment of hypertension for a long time, but the bioactive ingredients which responsible for their therapeutic effectiveness are remain unclear. Therefore, screening bioactive chemicals in natural sources is still the most straightforward strategy for novel Angiotensin-converting enzyme inhibitor (ACEi)-based anti-hypertension agents discovery. In this study, we demonstrated a bioactivity-guided fractionation strategy for identifying bioactive fractions and chemicals from pine needle based on LC/MS assay as well as elucidating their mechanisms of pharmacological activity. And we found out the compound in pine needle extracts being ACE-inhibitory active is catechin. When ACE activity was assayed in rat tissue membranes, it was observed that catechin demonstrate ACE inhibition in kidney, lung and testes tissue. All these presents catechin in pine needle could be a potential cardiovascular medicine.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/farmacologia , Anti-Hipertensivos/farmacologia , Catequina/farmacologia , Pinus/química , Extratos Vegetais/farmacologia , Inibidores da Enzima Conversora de Angiotensina/química , Animais , Anti-Hipertensivos/química , Captopril/química , Captopril/farmacologia , Catequina/química , Fracionamento Químico , Cromatografia Líquida , Ativação Enzimática/efeitos dos fármacos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Extratos Vegetais/química , Ratos
16.
Curr Med Chem ; 24(17): 1874-1891, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28578650

RESUMO

Snakes are fascinating creatures and have been residents of this planet well before ancient humans dwelled the earth. Venomous snakes have been a figure of fear, and cause notable mortality throughout the world. The venom constitutes families of proteins and peptides with various isoforms that make it a cocktail of diverse molecules. These biomolecules are responsible for the disturbance in fundamental physiological systems of the envenomed victim, leading to morbidity which can lead to death if left untreated. Researchers have turned these life-threatening toxins into life-saving therapeutics via technological advancements. Since the development of captopril, the first drug that was derived from bradykininpotentiating peptide of Bothrops jararaca, to the disintegrins that have potent activity against certain types of cancers, snake venom components have shown great potential for the development of lead compounds for new drugs. There is a continuous development of new drugs from snake venom for coagulopathy and hemostasis to anti-cancer agents. In this review, we have focused on different snake venom proteins / peptides derived drugs that are in clinical use or in developmental stages till to date. Also, some commonly used snake venom derived diagnostic tools along with the recent updates in this exciting field are discussed.


Assuntos
Venenos de Serpentes/química , Animais , Anticoagulantes/química , Anticoagulantes/metabolismo , Anticoagulantes/uso terapêutico , Batroxobina/química , Batroxobina/uso terapêutico , Coagulação Sanguínea/efeitos dos fármacos , Captopril/química , Captopril/uso terapêutico , Peptídeos/metabolismo , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Venenos de Serpentes/metabolismo , Serpentes/metabolismo , Trombose/tratamento farmacológico , Trombose/patologia , Tirofibana , Toxinas Biológicas/metabolismo , Toxinas Biológicas/farmacologia , Toxinas Biológicas/uso terapêutico , Tirosina/análogos & derivados , Tirosina/química , Tirosina/uso terapêutico
17.
Appl Opt ; 56(11): E58-E63, 2017 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-28414342

RESUMO

In this work, a combined flow injection-photo thermal lens microscopy (FI-PTLM) system was used for highly sensitive determination of captopril as an angiotensin-converting enzyme inhibitor. Captopril has no absorption in the visible range, but due to its thiol group could interact with gold nanoparticles (GNPs). GNPs, because of their surface plasmon resonance (SPR), have absorption in the visible range, but their interaction with a low concentration of captopril shows no effective change in UV-Vis spectrophotometry because their aggregation is slight. On the contrary, at the same condition, the PTLM with a visible light source enables sensitive measurement of this compound. The thiol group of captopril binds to the surface of GNPs and decreases the SPR. At the optimum condition in the focal volume of 2.68 fL (f=10-15), the obtained range of linearity was 50-800 nM. The developed method was successfully applied for the determination of captopril in human serum and pharmaceutical samples.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/análise , Captopril/análise , Ouro , Nanopartículas Metálicas/análise , Microscopia Eletrônica de Transmissão , Inibidores da Enzima Conversora de Angiotensina/sangue , Inibidores da Enzima Conversora de Angiotensina/química , Captopril/sangue , Captopril/química , Desenho de Equipamento , Humanos , Lentes , Luz , Nanopartículas Metálicas/química , Espectrofotometria/instrumentação , Espectrofotometria/métodos , Ressonância de Plasmônio de Superfície , Comprimidos/química
18.
Int J Nanomedicine ; 12: 2703-2716, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28435253

RESUMO

Antimicrobial photodynamic therapy (aPDT) has beneficial effects in dental treatment. We applied captopril-protected gold (Au25(Capt)18) clusters as a novel photosensitizer for aPDT. Photoexcited Au clusters under light irradiation generated singlet oxygen (1O2). Accordingly, the antimicrobial and cytotoxic effects of Au25(Capt)18 clusters under dental blue light-emitting diode (LED) irradiation were evaluated. 1O2 generation of Au25(Capt)18 clusters under blue LED irradiation (420-460 nm) was detected by a methotrexate (MTX) probe. The antimicrobial effects of photoexcited Au clusters (0, 5, 50, and 500 µg/mL) on oral bacterial cells, such as Streptococcus mutans, Aggregatibacter actinomycetemcomitans, and Porphyromonas gingivalis, were assessed by morphological observations and bacterial growth experiments. Cytotoxicity testing of Au clusters and blue LED irradiation was then performed against NIH3T3 and MC3T3-E1 cells. In addition, the biological performance of Au clusters (500 µg/mL) was compared to an organic dye photosensitizer, methylene blue (MB; 10 and 100 µg/mL). We confirmed the 1O2 generation ability of Au25(Capt)18 clusters through the fluorescence spectra of oxidized MTX. Successful application of photoexcited Au clusters to aPDT was demonstrated by dose-dependent decreases in the turbidity of oral bacterial cells. Morphological observation revealed that application of Au clusters stimulated destruction of bacterial cell walls and inhibited biofilm formation. Aggregation of Au clusters around bacterial cells was fluorescently observed. However, photoexcited Au clusters did not negatively affect the adhesion, spreading, and proliferation of mammalian cells, particularly at lower doses. In addition, application of Au clusters demonstrated significantly better cytocompatibility compared to MB. We found that a combination of Au25(Capt)18 clusters and blue LED irradiation exhibited good antimicrobial effects through 1O2 generation and biosafe characteristics, which is desirable for aPDT in dentistry.


Assuntos
Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Ouro/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Aggregatibacter actinomycetemcomitans/efeitos dos fármacos , Animais , Captopril/química , Captopril/farmacologia , Corantes , Ouro/química , Luz , Azul de Metileno/farmacologia , Camundongos , Células NIH 3T3/efeitos dos fármacos , Fármacos Fotossensibilizantes/química , Porphyromonas gingivalis/efeitos dos fármacos , Oxigênio Singlete/metabolismo , Streptococcus mutans/efeitos dos fármacos
19.
Mater Sci Eng C Mater Biol Appl ; 73: 472-477, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-28183634

RESUMO

A novel nanomaterial-based voltammetric sensor has been developed for use a highly sensitive tool for the simultaneous determination of captopril (CA), acetaminophen (AC), tyrosine (TY) and hydrochlorothiazide (HCTZ). The device is based on the application of NiO/CNTs and (2-(3,4-dihydroxyphenethyl)isoindoline-1,3-dione) (DPID) to modify carbon paste electrodes. The NiO/CNTs nanocomposite was synthesized through a direct chemical precipitation approach and was characterized with X-ray powder diffraction (XRD), and scanning electron microscopy (SEM). The NiO/CNTs/DPID/CPEs were found to facilitate the analysis of CA, AC, TY and HCTZ in the concentration ranges of 0.07-200.0, 0.8-550.0, 5.0-750.0 and 10.0-600.0µM with the respective detection limits of 9.0nM, 0.3µM, 1.0µM and 5.0µM. The developed NiO/CNTs/DPID/CPEs were used for the determination of the mentioned analytes in pharmaceutical and biological real samples.


Assuntos
Acetaminofen/análise , Captopril/análise , Técnicas Eletroquímicas/instrumentação , Hidroclorotiazida/análise , Nanoestruturas/química , Tirosina/análise , Acetaminofen/química , Captopril/química , Humanos , Hidroclorotiazida/química , Nanotubos de Carbono/química , Nanotubos de Carbono/ultraestrutura , Níquel/química , Oxirredução , Tirosina/química , Difração de Raios X
20.
Acta Pol Pharm ; 74(2): 527-541, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29624258

RESUMO

A microwave induced irradiation synthesis, was proposed for the preparation of hydroxypropyl methylcellulose-graft-(polyvinylalcohal-co-acrylic acid) hydrogels. The hydrogels were separately synthesized by using microwave irradiation method and conventional water bath heating method. Moreover, the prepared hydrogels were loaded with an antihypertensive drug, captopril. Chemical groups, thermal stability and surface morphology of these hydrogels were characterized by FT-IR, DSC and SEM. Swelling ratios of the gels were measured gravimetrically at'pH 1.2 and 7.4. Results showed that micrographs obtained from scanning electron microscopy (SEM), revealed that gels synthesized using microwave irradiation had more uniformly porous network structures. The uniformity in porosity was due to rapid and instantaneous penetration of microwave energy throughout the surface and they had higher swelling ratios in comparison to hydrogels synthesized by water bath method. Thermal analysis (DCS and TGA) depicted that crosslinked polymers were more stable. FT-IR analysis had confirmed the formation of the new polymeric network. X-ray diffractogram revealed that crystallinity of HPMC was reduced in hydrogel prepared by microwave radiation. It had also been observed that high crosslinking density diminish swelling of hydrogel. A stable network of hydroxypropyl methylcellulose (HPMC), poly(vinylalcohal) (PVA) and acrylic acid was developed in shorter time period under influence of microwave radiations.


Assuntos
Acrilatos/síntese química , Anti-Hipertensivos/química , Captopril/química , Portadores de Fármacos , Micro-Ondas , Polímeros/síntese química , Tecnologia Farmacêutica/métodos , Compostos de Vinila/síntese química , Varredura Diferencial de Calorimetria , Química Farmacêutica , Cristalografia por Raios X , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Hidrogéis , Concentração de Íons de Hidrogênio , Microscopia Eletrônica de Varredura , Porosidade , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de Superfície , Termogravimetria , Fatores de Tempo , Água/química
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