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Molecules ; 26(13)2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34206357


In the current work, a simple, economical, accurate, and precise HPLC method with UV detection was developed to quantify Favipiravir (FVIR) in spiked human plasma using acyclovir (ACVR) as an internal standard in the COVID-19 pandemic time. Both FVIR and ACVR were well separated and resolved on the C18 column using the mobile phase blend of methanol:acetonitrile:20 mM phosphate buffer (pH 3.1) in an isocratic mode flow rate of 1 mL/min with a proportion of 30:10:60 %, v/v/v. The detector wavelength was set at 242 nm. Maximum recovery of FVIR and ACVR from plasma was obtained with dichloromethane (DCM) as extracting solvent. The calibration curve was found to be linear in the range of 3.1-60.0 µg/mL with regression coefficient (r2) = 0.9976. However, with acceptable r2, the calibration data's heteroscedasticity was observed, which was further reduced using weighted linear regression with weighting factor 1/x. Finally, the method was validated concerning sensitivity, accuracy (Inter and Intraday's % RE and RSD were 0.28, 0.65 and 1.00, 0.12 respectively), precision, recovery (89.99%, 89.09%, and 90.81% for LQC, MQC, and HQC, respectively), stability (% RSD for 30-day were 3.04 and 1.71 for LQC and HQC, respectively at -20 °C), and carry-over US-FDA guidance for Bioanalytical Method Validation for researchers in the COVID-19 pandemic crisis. Furthermore, there was no significant difference for selectivity when evaluated at LLOQ concentration of 3 µg/mL of FVIR and relative to the blank.

Amidas/análise , Amidas/sangue , Antivirais/análise , Antivirais/sangue , Bioensaio/métodos , COVID-19/tratamento farmacológico , Cromatografia Líquida de Alta Pressão/métodos , Extração Líquido-Líquido/métodos , Pirazinas/análise , Pirazinas/sangue , Aciclovir/análise , Aciclovir/sangue , COVID-19/sangue , Calibragem , Estabilidade de Medicamentos , Congelamento , Humanos , Padrões de Referência , Reprodutibilidade dos Testes , Solventes/química
Sci Total Environ ; 761: 143229, 2021 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-33160673


Industrial processes generate toxic organic molecules that pollute environment water. Phenol and its derivative are classified among the major pollutant compounds found in water. They are naturally found in some industrial wastewater effluents. The removal of phenol compounds is therefore essential because they are responsible for severe organ damage if they exist above certain limits. In this study, ground Ziziphus leaves were utilized as adsorbents for phenolic compounds from synthetic wastewater samples. Several experiments were performed to study the effect of several conditions on the capacity of the Ziziphus leaves adsorbent, namely: the initial phenol concentration, the adsorbent concentration, temperature, pH value, and the presence of foreign salts (NaCl and KCl). The experimental results indicated that the adsorption process reached equilibrium in about 4 h. A drop in the amount of phenol removal, especially at higher initial concentration, was noticed upon increasing the temperature from 25 to 45 °C. This reflects the exothermic nature of the adsorption process. This was also confirmed by the calculated negative enthalpy of adsorption (-64.8 kJ/mol). A pH of 6 was found to be the optimum value at which the highest phenol removal occurred with around 15 mg/g at 25 °C for an initial concentration of 200 ppm. The presence of foreign salts has negatively affected the phenol adsorption process. The fitting of the experimental data, using different adsorption isotherms, indicated that the Harkins-Jura isotherm model was the best fit, evident by the high square of the correlation coefficient (R2) values greater than 0.96. The kinetic study revealed that the adsorption was represented by a pseudo-second-order reaction. The results of this study offer a basis to use Ziziphus leaves as promising adsorbents for efficient phenol removal from wastewater.

Poluentes Químicos da Água , Purificação da Água , Ziziphus , Adsorção , Concentração de Íons de Hidrogênio , Cinética , Fenol , Fenóis , Folhas de Planta/química , Água , Poluentes Químicos da Água/análise
Sci Total Environ ; 688: 1327-1334, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31726562


Olive mills wastewater (OMW) causes a serious environmental problem in the olive oil producing countries. This is due to its high organic matter content (COD), acidic pH values, suspended solids and high content of phytotoxic and antibacterial phenolic compounds. In this study, titanium dioxide (TiO2) as an adsorbent to reduce the COD value of the olive mill wastewater was investigated. Several variables were studied including the removal efficiency, effect of the initial COD value, amount of TiO2, temperature and pH value. The results revealed that the adsorption reached equilibrium within <120 min. Isotherm studies showed that the adsorption equilibrium data is in agreement with Freundlich isotherm. In addition, the results showed that the adsorption process was spontaneous and exothermic. The kinetic study indicated that adsorption did follow a pseudo-second order reaction. Variation of the amount of the TiO2 showed that using of 1.5 and 2 g/L of TiO2 caused the COD to drop from 1000 ppm to about 100 ppm (equilibrium concentration) in about 120 min. However, the use of 1 g/L of TiO2 exhibited almost the same effect on the COD-uptake, and the equilibrium concentration was about 400 ppm. The COD uptake was found to be inversely proportional with the temperature, pH value and the addition of salts such as sodium chloride (NaCl) and potassium chloride (KCl).

Bioorg Med Chem ; 25(15): 3911-3921, 2017 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-28583806


(1S,2E,4S,6R,7E,11E)-2,7,11-cembratriene-4,6-diol (1) and its 4-epi-analog (2) are diterpene precursors of the key flavor components in most Nicotiana (tobacco) species that purposely degraded during commercial tobacco fermentation. Angiogenesis, recruitment of new blood vessels, is important for tumor growth, survival and metastasis that can be targeted to control cancer. This study shows evidences and potential of the cembranoid 1 as a potent angiogenesis modulator through targeting VEGFR2. In silico study suggested favorable docking scores and binding affinity of 1 at the ATP binding pocket of VEGFR2. The binding mode of 1 was parallel to the standard FDA-approved antiangiogenic drug sunitinib (4). In vitro, cembranoid 1 significantly reduced the activated VEGFR2 levels in multiple breast cancer cell lines. Intraperitoneal 40mg/kg, 3X/week treatment of 1 significantly reduced the MDA-MB-231 cells breast tumor size in mice. Immunohistochemistry and Western blotting analysis of the treated mice tumors showed significant downregulation of the vasculogenesis marker CD31 and suppressed activated VEGFR2-paxillin-FAK pathway. Matrigel study in Swiss albino mice showed similar trend. The tobacco cembranoid 1 is a potential antiangiogenic lead useful for future use to control breast malignancies.

Inibidores da Angiogênese/farmacologia , Diterpenos/farmacologia , Tabaco/química , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
Bioorg Med Chem ; 24(22): 5748-5761, 2016 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-27681240


(1S,2E,4S,6R,7E,11E)-2,7,11-Cembratriene-4,6-diol (1) and its 4-epi-analog (2) are the cembranoid precursors to several key flavor ingredients in most Nicotiana (tobacco) species. Nearly 40-60% of 1 and 2 are purposely degraded during the commercial tobacco fermentation. However, 1 and 2 display promising bioactivities, including anticancer. Breast cancer is the most diagnosed cancer in women and ranked second female disease killer. The receptor tyrosine kinase c-Met correlates with aggressiveness of certain breast cancer phenotypes and thus considered a valid therapeutic target. This study reports the discovery and optimization of the tobacco-based cembranoid 1 as a novel c-Met inhibitory scaffold using combined structure- and ligand-based approaches. 1 displayed antiproliferative, anti-migratory and anti-invasive effects against the c-Met overexpressing MDA-MB-231 breast cancer cells at moderate µM concentrations. The Z'-LYTE kinase platform and Western blot analysis identified c-Met as a potential macromolecular target. Rationally designed carbamate analogs were proposed to probe additional targeted c-Met interactions and improve the cellular potency. The 6-phenyl carbamate 3 showed enhanced c-Met inhibitory activity. Structure-activity relationships of different substituents on the 3's phenyl moiety were studied. The most active analog 20 showed potent in vitro anticancer activity against the MDA-MB-231 breast cancer cells at low µM concentrations, with minimal toxicity on the non-tumorigenic MCF-10A mammary epithelial cells. Cembranoid 20 potently inhibited the c-Met catalytic activity in Z'-LYTE kinase assay and various cellular c-Met-driven signaling pathways. Furthermore, 20 displayed a robust antitumor activity in a breast cancer xenograft athymic mouse model and thus promoted to the lead rank. Cembranoids are novel c-Met inhibitors appropriate for future use to control c-Met dependent malignancies.

Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Diterpenos/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Diterpenos/síntese química , Diterpenos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Inibidores de Proteínas Quinases/síntese química , Inibidores de Proteínas Quinases/química , Proteínas Proto-Oncogênicas c-met/metabolismo , Relação Estrutura-Atividade
Biosens Bioelectron ; 77: 491-8, 2016 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-26457734


Currently used cancer marker for prostate adenocarcinoma (PC), serum prostate-specific antigen (PSA), greatly overestimates PC population. Patients with high PSA levels have to undergo unnecessary but physically painful and expensive procedure such as prostate biopsies repeatedly. The reliability of PC test can be greatly increased by finding a protein that is secreted selectively by malignant, but not normal, prostate cells. A recently discovered novel protein, referred as neuroendocrine marker (NEM), is secreted only by malignant prostate cells and released in blood circulation. Although NEM seems to be significantly more reliable based on the data obtained from a limited cohort, currently available NEM ELISA is not suitable for undertaking a large study. Therefore, the goal of the present study was to develop an alternative, label-free assay system that can reliably measure NEM and PSA in patient samples. Herein an optofluidic chip that can reliably detect PSA as well as NEM in patient samples has been developed. The optofluidic chip, which consists of arrayed nanopore-based sensors fabricated from anodic aluminum oxide (AAO) thin film, offers improved sensitivity upon the optimization of the concentration of the detector antibodies immobilized on the sensor surface. The results demonstrate that the chip is reliable, extremely sensitive and requires just 1 µl of patient serum (or even less) to measure PSA and NEM even in a non-cancer individual. Compared with the traditional ELISA for PSA, the nanopore-based sensor assay is 50-100 fold more sensitive, and offers many advantages such as elimination of labeled antigen, need for sophisticated equipment and highly trained individuals. These advantages, along with the low cost, should make the technology suitable for point-of-care application to screen elderly male populations for PC and to monitor the progress of patients undergoing PC treatment.

Biomarcadores Tumorais/sangue , Imunoensaio/instrumentação , Dispositivos Lab-On-A-Chip , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Ressonância de Plasmônio de Superfície/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Humanos , Masculino , Membranas Artificiais , Nanoporos/ultraestrutura , Dispositivos Ópticos , Neoplasias da Próstata/diagnóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade