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1.
Int J Biol Macromol ; 269(Pt 2): 132200, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38723834

RESUMEN

Viral infections continue to pose a significant global public health threat. Targeting host proteins, such as cluster of differentiation (CD) macromolecules, may offer a promising alternative approach to developing antiviral treatments. CDs are cell-surface biological macromolecules mainly expressed on leukocytes that viruses can use to enter cells, thereby evading immune detection and promoting their replication. The manipulation of CDs by viruses may represent an effective and clever means of survival through the prolonged co-evolution of hosts and viruses. Targeting of CDs is anticipated to hinder the invasion of related viruses, modulate the body's immune system, and diminish the incidence of subsequent inflammation. They have become crucial for biomedical diagnosis, and some have been used as valuable tools for resisting viral infections. However, a summary of the structures and functions of CDs involved in viral infection is currently lacking. The development of drugs targeting these biological macromolecules is restricted both in terms of their availability and the number of compounds currently identified. This review provides a comprehensive analysis of the critical role of CD proteins in virus invasion and a list of relevant targeted antiviral agents, which will serve as a valuable reference for future research in this field.


Asunto(s)
Antivirales , Virosis , Humanos , Antivirales/farmacología , Antivirales/uso terapéutico , Antivirales/química , Virosis/tratamiento farmacológico , Virosis/virología , Virus/efectos de los fármacos , Animales , Interacciones Huésped-Patógeno
2.
J Cell Mol Med ; 28(8): e18265, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38534098

RESUMEN

Mitochondria and their related genes (MTRGs) are pivotal in the tumour microenvironment (TME) of cervical cancer, influencing prognosis and treatment response. This study developed a prognostic model using MTRGs to predict overall survival (OS) in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC), aiming for personalized therapy. Analysing 14 MTRGs like ISCU and NDUFA11 through techniques such as univariate Cox regression, we found that a low mitochondrial (MT) score is associated with better survival, while a high MT score predicts poorer outcomes. The TME score, particularly influenced by CD8 T cells, also correlates with prognosis, with a high score indicating favourable outcomes. The interplay between MT and TME subtypes revealed that the best prognosis is seen in patients with a low MT and high TME score. Our findings highlight the role of MTRGs as potential biomarkers and therapeutic targets in cervical cancer, offering a novel approach to improving patient outcomes through a more nuanced understanding of mitochondrial function and immune interactions within the TME. This model presents a promising avenue for enhancing the precision of prognostic assessments in CESC.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias del Cuello Uterino , Humanos , Femenino , Microambiente Tumoral , Mitocondrias , ADN Mitocondrial
3.
Foods ; 13(2)2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38275686

RESUMEN

In this study, a highly sensitive monoclonal antibody (mAb) was developed for the detection of aflatoxin B1 (AFB1) in maize and feed. Additionally, indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and time-resolved fluorescence immunoassay assay (TRFICA) were established. Firstly, the hapten AFB1-CMO was synthesized and conjugated with carrier proteins to prepare the immunogen for mouse immunization. Subsequently, mAb was generated using the classical hybridoma technique. The lowest half-maximal inhibitory concentration (IC50) of ic-ELISA was 38.6 ng/kg with a linear range of 6.25-100 ng/kg. The limits of detections (LODs) were 6.58 ng/kg and 5.54 ng/kg in maize and feed, respectively, with the recoveries ranging from 72% to 94%. The TRFICA was developed with a significantly reduced detection time of only 21 min, from sample processing to reading. Additionally, the limits of detection (LODs) for maize and feed were determined to be 62.7 ng/kg and 121 ng/kg, respectively. The linear ranges were 100-4000 ng/kg, with the recoveries ranging from 90% to 98%. In conclusion, the development of AFB1 mAb and the establishment of ic-ELISA for high-throughput sample detection, as well as TRFICA for rapid detection presented robust tools for versatile AFB1 detection in different scenarios.

4.
Metabolites ; 13(8)2023 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-37623842

RESUMEN

Because of the high research and development cost of new drugs, the long development process of new drugs, and the high failure rate at later stages, combining past drugs has gradually become a more economical and attractive alternative. However, the ensuing problem of drug-drug interactions (DDIs) urgently need to be solved, and combination has attracted a lot of attention from pharmaceutical researchers. At present, DDI is often evaluated and investigated from two perspectives: pharmacodynamics and pharmacokinetics. However, in some special cases, DDI cannot be accurately evaluated from a single perspective. Therefore, this review describes and compares the current DDI evaluation methods based on two aspects: pharmacokinetic interaction and pharmacodynamic interaction. The methods summarized in this paper mainly include probe drug cocktail methods, liver microsome and hepatocyte models, static models, physiologically based pharmacokinetic models, machine learning models, in vivo comparative efficacy studies, and in vitro static and dynamic tests. This review aims to serve as a useful guide for interested researchers to promote more scientific accuracy and clinical practical use of DDI studies.

5.
Metabolites ; 13(4)2023 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-37110187

RESUMEN

There is often abuse of drugs in livestock and poultry production, and the improper use of drugs leads to the existence of a low level of residues in eggs, which is a potential threat to human safety. Enrofloxacin (EF) and tilmicosin (TIM) are regularly combined for the prevention and treatment of poultry diseases. The current studies on EF or TIM mainly focus on a single drug, and the effects of the combined application of these two antibiotics on EF metabolism in laying hens are rarely reported. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the residual EF and TIM in laying hens and to investigate the effect of TIM on the EF metabolism in laying hens. In this paper, we first establish a method that can detect EF and TIM simultaneously. Secondly, the results showed that the highest concentration of EF in the egg samples was 974.92 ± 441.71 µg/kg on the 5th day of treatment. The highest concentration of EF in the egg samples of the combined administration group was 1256.41 ± 226.10 µg/kg on the 5th day of administration. The results showed that when EF and TIM were used in combination, the residue of EF in the eggs was increased, the elimination rate of EF was decreased, and the half-life of EF was increased. Therefore, the use of EF and TIM in combination should be treated with greater care and supervision should be strengthened to avoid risks to human health.

6.
Biochimie ; 206: 1-11, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36179939

RESUMEN

Nucleic acids are an indispensable component in all known life forms. The biological processes are regulated by Nucleic acids, which associate to form special high-order structures. since the high-level structures of nucleic acids are related to gene expression in cancer cells or viruses, it is very likely to become a potential drug target. Traditional biochemical methods are limited to distinguish the conformational distribution and dynamic transition process of single nucleic acid structure. The ligands based on the intermediate and transition states between different conformations are not designed by traditional biochemical methods. The single-molecule techniques enable real-time observation of the individual nucleic acid behavior due to its high resolution. Here, we introduce the application of single-molecule techniques in the study of small molecules to recognize nucleic acid structures, such as single-molecule FRET, magnetic tweezers, optical tweezers and atomic force microscopy. At the same time, we also introduce the specific advantages of single-molecule technology compared with traditional biochemical methods and some problems arisen in current research.


Asunto(s)
Ácidos Nucleicos , Virus , Nanotecnología/métodos , Microscopía de Fuerza Atómica/métodos , Conformación Molecular , Conformación de Ácido Nucleico
7.
Pharmaceutics ; 14(10)2022 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-36297496

RESUMEN

Glaesserella parasuis (G. parasuis) causes Glasser's disease in pigs and causes high mortality in piglets. The new drug Aditoprim (ADP) alone or combined with Sulfamethoxazole (SMZ) is one of the good choices for treating respiratory infections. The objective of this study was to recommend the optimal dosing regimen for the treatment of G. parasuis infection which contains resistance and virulence genes by ADP/SMZ compound through pharmacokinetics-pharmacodynamics (PK-PD) modeling. The whole genome of the virulent strain G. parasuis H78 was obtained and annotated by whole genome sequencing. The results show that G. parasuis H78 consists of a unilateral circular chromosome with prophages in the genome. The annotation results of G. parasuis H78 showed that the genome contained a large number of virulence-related genes and drug resistance-related genes. The in vitro PD study showed that the antibacterial effect of ADP/SMZ compound against G. parasuis was time-dependent, and AUC/MIC was selected as the PK-PD modeling parameter. The PK study showed that the content of ADP/SMZ compound in pulmonary epithelial lining fluid (PELF) was higher than plasma, and there were no significant differences in ADP and SMZ PK parameters between the healthy and infected group. The dose equation to calculate the optimal dosing regimen of ADP/SMZ compound administration for control of G. parasuis infection was 5/25 mg/kg b.w., intramuscular injection once a day for 3~5 consecutive days. The results of this study provide novel therapeutic options for the treatment of G. parasuis infection to decrease the prevalence and disease burden caused by G. parasuis.

8.
Res Vet Sci ; 148: 33-41, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35660543

RESUMEN

The monitoring results in China have shown that the phenomenon of single-pollutant residues exceeding the standard in food has decreased, while the coexistence of many low-level residual pollutants has increased significantly. Among these, the combined use of enrofloxacin (EF) and tilmicosin (TIM) is serious. Despite that, little is comprehended about influences of the drug-drug interactions (DDIs) caused by EF and TIM. The purpose of this work is to evaluate the effects caused by the combination of these two drugs on metabolism and residues in vivo and in vitro. The results showed that TIM affected the metabolism of EF by inhibiting CYP3A4 and increased the residual concentrations of EF in broilers. Moreover, the time of elimination of EF was prolonged. Thus, the combined use of TIM and EF must be reduced in veterinary drugs and feeds in order to ensure the safety of humans and animals.


Asunto(s)
Citocromo P-450 CYP3A , Fluoroquinolonas , Animales , Antibacterianos/farmacología , Pollos , Interacciones Farmacológicas , Enrofloxacina , Fluoroquinolonas/farmacología , Tilosina/análogos & derivados
9.
Antibiotics (Basel) ; 11(3)2022 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-35326865

RESUMEN

The study was to explore the rational use of danofloxacin against Mycoplasma gallisepticum (MG) based on its clinical breakpoint (CBP) and the effect on lung microbiota. The CBP was established according to epidemiological cutoff value (ECV/COWT), pharmacokinetic-pharmacodynamic (PK-PD) cutoff value (COPD) and clinical cutoff value (COCL). The ECV was determined by the micro-broth dilution method and analyzed by ECOFFinder software. The COPD was determined according to PK-PD modeling of danofloxacin in infected lung tissue with Monte Carlo analysis. The COCL was performed based on the relationship between the minimum inhibitory concentration (MIC) and the possibility of cure (POC) from clinical trials. The CBP in infected lung tissue was 1 µg/mL according to CLSI M37-A3 decision tree. The 16S ribosomal RNA (rRNA) sequencing results showed that the lung microbiota, especially the phyla Firmicutes and Proteobacteria had changed significantly along with the process of cure regimen (the 24 h dosing interval of 16.60 mg/kg b.w for three consecutive days). Our study suggested that the rational use of danofloxacin for the treatment of MG infections should consider the MIC and effect of antibiotics on the respiratory microbiota.

10.
Metabolites ; 13(1)2022 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-36676982

RESUMEN

Sulfamethoxazole (SMZ), as a sulfa antibiotic, is often used in the treatment of various infectious diseases in animal husbandry. At present, SMZ still has many unresolved problems in the material balance, metabolic pathways, and residual target tissues in food animals. Therefore, in order to solve these problems, the metabolism, distribution, and elimination of SMZ is investigated in pigs, chickens, and rats by radioactive tracing methods, and the residue marker and target tissue of SMZ in food animals were determined, providing a reliable basis for food safety. After a single administration of [3H]-SMZ (rats and pigs by intramuscular injection and chickens by oral gavage), the total radioactivity was rapidly excreted, with more than 93% of the dose excreted within 14 days in the three species. Pigs and rats had more than 75% of the administered volume recovered by urine. After 7 days of continuous administration, within the first 6 h, radioactivity was found in almost all tissues. The highest radioactivity and longest persistence in pigs was in the liver, while in chickens it was in the liver and kidneys, most of which was removed within 14 days. A total of six, three and three metabolites were found in chickens, rats and pigs, respectively. N4-acetyl-sulfamethoxazole (S1) was the main metabolite of SMZ in rats, pigs and chickens. The radioactive substance with the longest elimination half-life is sulfamethoxazole (S0), so S0 was suggested to be the marker residue in pigs and chickens.

11.
Front Pharmacol ; 12: 754876, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34899308

RESUMEN

Illegal use of salbutamol (SAL), a ß-adrenergic leanness-enhancing agent, has posed potential threat to human health in China. The excretion and depletion of SAL in pigs and goats were investigated, and the concentration correlations between edible tissues and living samples were analyzed to find out a suitable living sample for pre-slaughter monitoring of SAL in pigs and goats. After a single oral dosage of 1.2 mg/kg SAL, approximately 70% of the dose was excreted by pigs and goats from their excreta. When pigs and goats were supplied feed containing SAL (20 mg/kg) for 14 consecutive days, high concentrations of SAL were observed in the liver and kidneys, and the longest persistence was observed in hair. Unlike pigs, SAL was presented primarily as conjugated SAL in goats. Excellent concentration correlations of SAL were observed between urine and edible tissues both in pigs and goats, and in addition, good correlations also were found between hair and edible tissues in pigs and between feces and edible tissues in goats. Hence, urine and hair could accurately predict SAL concentrations in edible tissues of pigs, whereas feces and urine were satisfactory for predicting SAL concentrations in edible tissues of goats. These data make it possible for pre-slaughter monitoring of SAL residues in the edible tissues of pigs and goats.

12.
Front Microbiol ; 12: 712473, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34566919

RESUMEN

The aim of this study was to explore the prudent use of tylosin for the treatment of chronic respiratory infectious diseases in chickens caused by Mycoplasma gallisepticum (MG) based on its clinical breakpoint (CBP) and its effect on lung microbiota. The CBP was established based on the wild-type/epidemiological cutoff value (COWT/ECV), pharmacokinetics-pharmacodynamics (PK-PD) cutoff value (COPD), and clinical cutoff value (COCL) of tylosin against MG. The minimum inhibitory concentration (MIC) of tylosin against 111 MG isolates was analyzed and the COWT was 2 µg/ml. M17 with MIC of 2 µg/ml was selected as a representative strain for the PK-PD study. The COPD of tylosin against MG was 1 µg/ml. The dosage regimen formulated by the PK-PD study was 3 days administration of tylosin at a dose of 45.88 mg/kg b.w. with a 24-h interval. Five different MIC MGs were selected for clinical trial, and the COCL of tylosin against MG was 0.5 µg/ml. According to the CLSI decision tree, the CBP of tylosin against MG was set up as 2 µg/ml. The effect of tylosin on lung microbiota of MG-infected chickens was analyzed by 16S rRNA gene sequencing. Significant change of the lung microbiota was observed in the infection group and treatment group based on the principal coordinate analysis and the Venn diagrams of the core and unique OTU. The phyla Firmicutes and Proteobacteria showed difference after MG infection and treatment. This study established the CBP of tylosin against MG. It also provided scientific data for the prudent use of tylosin based on the evaluation of MG infection and tylosin treatment on the lung microbiota.

13.
Artículo en Inglés | MEDLINE | ID: mdl-34097576

RESUMEN

Sulphonamides (SAs) are widely used in animal husbandry. In our work, based on multi-walled carbon nanotubes, a novel residue method was developed for highly sensitive and determination trace levels of sulfamethoxazole, acetyl sulfamethoxazole and aditoprim in edible swine tissues by LC-MS/MS with magnetic solid-phase extraction. The samples were extracted using 2% ammoniated acetonitrile and purified by magnetic solid phase extraction (MSPE). Under the optimal conditions, good linearity was obtained ranging from 5 to 160 µg kg-1. The limits of detection (LOD) and quantification (LOQ) were 2 µg kg-1 and 5 µg kg-1 respectively. The average recoveries were 73.9-94.8% at different spiking levels. The inter-day RSDs were 6.2-10.7% and the intra-day RSDs were 2.4-5.4%. MSPE based on multi-walled carbon nanotubes was a simple and efficient method to enrich and separate the analyses and could be successfully applied for extraction of sulfamethoxazole, acetyl sulfamethoxazole and aditoprim residues in swine tissues.


Asunto(s)
Nanotubos de Carbono/química , Extracción en Fase Sólida/métodos , Sulfametoxazol/análisis , Extractos de Tejidos/análisis , Trimetoprim/análogos & derivados , Animales , Cromatografía Líquida de Alta Presión , Residuos de Medicamentos/análisis , Contaminación de Alimentos/análisis , Humanos , Límite de Detección , Fenómenos Magnéticos , Porcinos , Espectrometría de Masas en Tándem , Trimetoprim/análisis , Drogas Veterinarias/análisis
14.
Bioorg Chem ; 110: 104804, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33740677

RESUMEN

Extensive evidence indicates that RNA G-quadruplexes have associated with some important cellular events. Investigation of RNA G-quadruplexes is thus vital to revealing their biofunctions. Several small molecules have been developed to target RNA G-quadruplexes to date. Some of the small molecules showed significantly light-up fluorescence signals upon binding to RNA G-quadruplexes, while some of them regulated the biofunctions of RNA G-quadruplexes. In this mini-review, the small molecules divided into four kinds are expounded which focused mainly on their structural features and biological activities. Moreover, we raised the current challenges and promising prospects. This mini-review might contribute to exploiting more sophisticated small molecules targeting RNA G-quadruplexes with high specificity based on the reported chemical structural features.


Asunto(s)
Desarrollo de Medicamentos , ARN/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/farmacología , Relación Dosis-Respuesta a Droga , G-Cuádruplex/efectos de los fármacos , Estructura Molecular , Bibliotecas de Moléculas Pequeñas/síntesis química , Bibliotecas de Moléculas Pequeñas/química , Relación Estructura-Actividad
15.
Curr Drug Deliv ; 18(2): 224-233, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32885750

RESUMEN

OBJECTIVE: A ceftiofur hydrochloride long-acting oily suspension with no irritation was prepared by testing and optimizing the types and amounts of organic solvents, suspending agents, and surfactants. METHODS: Its properties, stability, injection site irritation, in vitro release, and pharmacokinetics in pigs were evaluated. The optimum formulation was used ethyl oleate, aluminum monosterate, and span-80 as organic solvents, suspending agents, and surfactant, respectively. The drug microparticles were uniform long strip with size of 1.53 ± 0.11 µm and no agglomerations, and were evenly dispersed. The re-dispersed time, sedimentation rate and pH value of the suspension were 4 s under a magnetic shaker rotating at 20 r/min, 1 and 5.0, respectively. It could go through 7-gage needle smoothly with withdrawal volume of 9.9 mL/min. RESULTS: The suspension showed good stability when stored away from light, no irritation at the injection site and sustained release in PBS buffer. After intramuscular administration, the drug concentration above 0.15 µg/mL was last for 120 h. Its elimination half-life (T1/2ke), mean residence time (MRT), and bioavailability were increased by 1.73, 1.62, and 2.16 times compared to Excenel®. CONCLUSION: The results suggested that the suspension had excellent sustained-release and will make ceftiofur hydrochloride more effective and convenient to use.


Asunto(s)
Antibacterianos , Cefalosporinas , Animales , Disponibilidad Biológica , Inyecciones Intramusculares , Suspensiones , Porcinos
16.
Food Chem ; 339: 127580, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-32858380

RESUMEN

In this study, a microbiological inhibition method for rapidly screening antibiotics in swine urine was established with an easy sample pre-treatment. The microbiological system consisted of an agar medium mixed with nutrients, sensitizers, a test bacterium (Geobacillus stearothermophilus ATCC12980) and pH indicator (bromocresol purple). It was observed that the detection limits of the test kit for twenty-eight common antimicrobial residues in urine, including ß-lactams, aminoglycosides, tetracyclines, sulfonamides, macrolides, and lincosamides, were less than or equal to the maximum residue limits of the kidney, as determined by the EU and China. Moreover, the false negative rate and the false positive rate, along with other performance indexes such as interassay coefficients of variation and shelf life of the kit, all met the standard requirements of the ISO13969:2003 guidelines. Additionally, our results were consistent with those using the gold-standard physical chemistry method, which suggest the proposed method is suitable for screening antibiotic residues.


Asunto(s)
Antibacterianos/orina , Residuos de Medicamentos/análisis , Ensayos Analíticos de Alto Rendimiento/métodos , Drogas Veterinarias/orina , Aminoglicósidos/farmacología , Aminoglicósidos/orina , Animales , Antibacterianos/análisis , Antibacterianos/farmacología , Medios de Cultivo , Reacciones Falso Negativas , Reacciones Falso Positivas , Contaminación de Alimentos/análisis , Geobacillus stearothermophilus/efectos de los fármacos , Límite de Detección , Macrólidos/farmacología , Macrólidos/orina , Sensibilidad y Especificidad , Sulfonamidas/farmacología , Sulfonamidas/orina , Porcinos , Tetraciclinas/farmacología , Tetraciclinas/orina , Drogas Veterinarias/farmacología
17.
Curr Drug Metab ; 21(12): 928-937, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32807049

RESUMEN

As a kind of haemoglobin, cytochrome P450 enzymes (CYP450) participate in the metabolism of many substances, including endogenous substances, exogenous substances and drugs. It is estimated that 60% of common prescription drugs require bioconversion through CYP450. The influence of macrolides on CYP450 contributes to the metabolism and drug-drug interactions (DDIs) of macrolides. At present, most studies on the effects of macrolides on CYP450 are focused on CYP3A, but a few exist on other enzymes and drug combinations, such as telithromycin, which can decrease the activity of hepatic CYP1A2 and CYP3A2. This article summarizes some published applications of the influence of macrolides on CYP450 and the DDIs of macrolides caused by CYP450. And the article may subsequently guide the rational use of drugs in clinical trials. To a certain extent, poisoning caused by adverse drug interactions can be avoided. Unreasonable use of macrolide antibiotics may enable the presence of residue of macrolide antibiotics in animal-origin food. It is unhealthy for people to eat food with macrolide antibiotic residues. So it is of great significance to guarantee food safety and protect the health of consumers by the rational use of macrolides. This review gives a detailed description of the influence of macrolides on CYP450 and the DDIs of macrolides caused by CYP450. Moreover, it offers a perspective for researchers to further explore in this area.


Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Interacciones Farmacológicas , Macrólidos/farmacocinética , Animales , Humanos
18.
Front Chem ; 8: 598, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32850634

RESUMEN

Tuberculosis and fungal infections can pose serious threats to human health. In order to find novel antimicrobial agents, 26 novel quinoxaline-1,4-di-N-oxides containing a thiazolidinone moiety were designed and synthesized, and their antimycobacterial activities were evaluated. Among them, compounds 2t, 2u, 2y, and 2z displayed the most potent antimycobacterial activity against Mycobacterium tuberculosis strain H37Rv (minimal inhibitory concentration [MIC] = 1.56 µg/mL). The antifungal activity of all the compounds was also evaluated against Candida albicans, Candida tropicalis, Aspergillus fumigatus, and Cryptococcus neoformans. Compounds 2t, 2u, 2y, and 2z exhibited potential antifungal activities, with an MIC between 2 and 4 µg/mL. Comparative molecular field analysis (CoMFA: q 2 = 0.914, r 2 = 0.967) and comparative molecular similarity index analysis (CoMSIA: q 2 = 0.918, r 2 = 0.968) models were established to investigate the structure and antimycobacterial activity relationship. The results of contour maps revealed that electronegative and sterically bulky substituents play an important role in the antimycobacterial activity. Electronegative and sterically bulky substituents are preferred at the C7 position of the quinoxaline ring and the C4 position of the phenyl group to increase the antimycobacterial activity. Additionally, more hydrogen bond donor substituents should be considered at the C2 side chain of the quinoxaline ring to improve the activity.

19.
Colloids Surf B Biointerfaces ; 194: 111196, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32599504

RESUMEN

Four fatty acid-solid lipid nanoparticles (SLNs) were formulated and evaluated for intracellular delivery, accumulation, as well as discrepancy in antimicrobial efficacy of their loaded enrofloxacin by using RAW 264.7 cells. The delivery efficacy of enrofloxacin into the macrophages by docosanoic acid SLNs (DAS), octadecanoic acid SLNs (OAS), hexadecanoic acid SLNs (HAS), and tetradecanoic acid SLNs (TAS) were 26.1-29.0, 9.3-10.3, 4.7-5.3 and 4.5-5.0 folds, respectively, compared to free drug when co-incubation for 0.25-4 h. The longer fatty acid prepared nanoparticles loaded enrofloxacin eliminated more slowly and accumulated in the cells for a longer time.The confocal microscopy also demonstrated that higher amount of fatty acid SLNs entered the cells with stronger accumulation performance and less amount SLNs absorbed on the cytomembrane as the carbon chain of fatty acids increased. The bactericidal activity of the four fatty acid SLNs against intracellular Salmonella CVCC541 significantly enhanced compared to the free enrofloxacin. These results revealed that fatty acid SLNs, especially docosanoic acid nanoparticles, might be effective nanocarriers to ferry enrofloxacin or other lipid soluble drugs into cells for intracellular bacterial infection treatment.


Asunto(s)
Lípidos , Nanopartículas , Antibacterianos/farmacología , Portadores de Fármacos , Enrofloxacina , Ácidos Grasos , Tamaño de la Partícula
20.
Int J Mol Sci ; 21(9)2020 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-32392795

RESUMEN

In antibiotics, ß-lactam is one kind of major concern acknowledged as an unavoidable contaminant in milk. Thus, a facile and sensitive method is essential for rapid ß-lactam antibiotics detection. In our work, a specific electrochemical receptor sensor based on the graphene/thionine (GO/TH) composite was established. The mechanism of the electrochemical receptor sensor was a direct competitive inhibition of the binding of horseradish peroxidase-labeled ampicillin (HRP-AMP) to the mutant BlaR-CTD protein by free ß-lactam antibiotics. Then, horseradish peroxidase (HRP) catalyzed the hydrolysis of the substrate hydrogen peroxide (H2O2), which produced an electrochemical signal. Under optimal experimental conditions, this method could quantitatively detect cefquinome from 0.1 to 8 µg L-1 and with the limit of detection (LOD) of 0.16 µg L-1, much lower than the maximum residue limit (MRL) of 5 µg L-1 set by the European Union. In addition, the LOD of spiked milk samples with cefalexin, cefquinoxime, cefotafur, penicillin G and ampicillin were 14.88 µg L-1, 2.46 µg L-1, 17.16 µg L-1, 0.06 µg L-1, 0.21 µg L-1 and the limits of quantitation (LOQ) were 36.09 µg L-1, 5.40 µg L-1, 41.45 µg L-1, 0.13 µg L-1, 0.42 µg L-1, respectively. The sensor showed a favorable recovery of 84.89-102.44%. Moreover, the electrochemical receptor sensor was successfully applied to assay ß-lactam antibiotics in milk, which showed good correlation with the results obtained from liquid chromatography-tandem mass spectrometry (LC-MS/MS).


Asunto(s)
Antibacterianos/análisis , Técnicas Biosensibles/métodos , Leche/química , beta-Lactamas/análisis , Animales , Cromatografía Liquida , Residuos de Medicamentos/análisis , Técnicas Electroquímicas , Contaminación de Alimentos/análisis , Grafito/química , Peroxidasa de Rábano Silvestre/metabolismo , Peróxido de Hidrógeno/metabolismo , Hidrólisis , Límite de Detección , Fenotiazinas/química , Espectrometría de Masas en Tándem
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