Coumarin belongs to a class of lactones that are fundamentally comprised of a benzene ring fused to an α-pyrone ring; these lactones are known as benzopyrones. Similarly, coumarin has a conjugated electron-rich framework and good charge-transport properties. Plants produce coumarin as a chemical response to protect themselves from predation. Coumarins are used in different products, such as cosmetics, additives, perfumes, aroma enhancers in various tobaccos and some alcoholic drinks, and they play a relevant role in natural products and in organic and medicinal chemistry. In addition, as candidate drugs, many coumarin compounds have strong pharmacological activity, low toxicity, high bioavailability and better curative effects and have been used to treat various types of diseases. Various endeavors were made to create coumarin-based anticoagulant, antimicrobial, antioxidant, anticancer, antidiabetic, antineurodegenerative, analgesic and anti-inflammatory agents. A class of chemical compounds called furocoumarins has phototoxic properties and is naturally synthesized via the fusion of coumarin to a furan ring in different plant species. Psoralens belong to the furocoumarin class and occur naturally in various plants, e.g., lemons, limes, and parsnips. Angelicin is an isomer of psoralens, and most furocoumarins, e.g., xanthotoxin, bergapten, and nodekenetin, are derivatives of psoralens or angelicin. The present work demonstrated that psoralen molecules exhibit anti-tumoral activity against breast cancer and influence different intracellular signals to maintain the high survival of breast cancer cells. Psoralens perform different functions, e.g., antagonize metabolic pathways, protease enzymes, and cell cycle progression and even interfere in the crosslinking between receptors and growth factor mitogenic signaling.
- MeSH
- analgetika chemie farmakologie MeSH
- antiinfekční látky chemie farmakologie MeSH
- antituberkulotika chemie farmakologie MeSH
- antitumorózní látky chemie farmakologie MeSH
- fikusin chemie farmakologie MeSH
- hypoglykemika chemie farmakologie MeSH
- lidé MeSH
- molekulární struktura MeSH
- neuroprotektivní látky chemie farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
An electrophoretic apparatus with a flow-gating interface has been developed, enabling hydrodynamic sequence injection of the sample into the separation capillary from the liquid flow by underpressure generated in the outlet electrophoretic vessel. The properties of the apparatus were tested on an artificial sample of an equimolar mixture of 100μM potassium and sodium ions and arginine. The repeatability of the injection of the tested ions expressed as RSD (in%) for the peak area, peak height and migration time was in the range 0.76-2.08, 0.18-0.68 and 0.28-0.48, respectively. Under optimum conditions, the apparatus was used for sequence monitoring of the reaction between the antidiabetic drug phenyl biguanide and the glycation agent methyl glyoxal. The reaction solution was continuously sampled by a microdialysis probe from a thermostated external vessel using a syringe pump at a flow rate of 3μLmin(-1) and was injected into a separation capillary at certain time intervals. The electrophoretic separation progressed in a capillary with an internal diameter of 50μm with a length of 11.5cm and was monitored using a contactless conductivity detector.
AIM: To evaluate the efficacy and safety of twice-daily insulin degludec/insulin aspart vs. twice-daily biphasic insulin aspart 30 in people with Type 2 diabetes mellitus who were naïve to insulin. METHODS: In this 26-week, multinational, open-label, controlled, two-arm, parallel-group, treat-to-target trial, participants [mean (± sd) age 58.9 (±8.9) years, duration of diabetes 9.5 (±5.9) years, HbA1c 68 (±8.7) mmol/mol or 8.4 (±0.8)% and BMI 31.2 (±4.2) kg/m(2) ) were randomized (1:1) to insulin degludec/insulin aspart (n = 197) or biphasic insulin aspart 30 (n = 197), administered with breakfast and the main evening meal, titrated to a self-monitored plasma glucose target > 3.9 and ≤ 5.0 mmol/l. RESULTS: The mean HbA1c was reduced to 49 mmol/mol (6.6%) with insulin degludec/insulin aspart and 48 mmol/mol (6.5%) with biphasic insulin aspart 30. Insulin degludec/insulin aspart achieved the prespecified non-inferiority margin (estimated treatment difference 0.02%; 95% CI -0.12, 0.17). Insulin degludec/insulin aspart was superior in lowering fasting plasma glucose (estimated treatment difference -1.00 mmol/l; 95% CI -1.4, -0.6; P < 0.001) and reducing overall and nocturnal confirmed hypoglycaemia at a similar overall insulin dose compared with biphasic insulin aspart 30. Similar proportions of participants in each arm experienced severe hypoglycaemia. Adverse events were equally distributed. CONCLUSIONS: Consistent with previous findings, insulin degludec/insulin aspart twice daily effectively improved long-term glycaemic control, with superior reductions in FPG, and significantly less overall and nocturnal confirmed hypoglycaemia compared with biphasic insulin aspart 30 in people with Type 2 diabetes who were insulin-naïve.
- MeSH
- bifázický inzulin aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- diabetes mellitus 2. typu krev farmakoterapie MeSH
- dlouhodobě působící inzulin aplikace a dávkování škodlivé účinky chemie terapeutické užití MeSH
- fixní kombinace léků MeSH
- glykovaný hemoglobin analýza MeSH
- hyperglykemie prevence a kontrola MeSH
- hypoglykemie chemicky indukované epidemiologie patofyziologie prevence a kontrola MeSH
- hypoglykemika aplikace a dávkování škodlivé účinky chemie terapeutické užití MeSH
- inzulin aspart aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- jídla MeSH
- krevní glukóza analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- monitorování léčiv MeSH
- NPH inzulin aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- riziko MeSH
- rozpustnost MeSH
- rozvrh dávkování léků MeSH
- selfmonitoring glykemie MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
Diabetes is one of the most widespread diseases characterized by a deficiency in the production of insulin or its ineffectiveness. As a result, the increased concentrations of glucose in the blood lead not only to damage to many of the body's systems but also cause the nonenzymatic glycation of plasma proteins affecting their drug binding. Since the binding ability influences its pharmacokinetics and pharmacodynamics, this is a very important issue in the development of new drugs and personalized medicine. In this study, capillary electrophoresis-frontal analysis was used to evaluate the affinities between human serum albumin or its glycated form and the first generation of sulfonylurea antidiabetics, since their inadequate concentration may induce hypoglycaemia or on the contrary hyperglycaemia. The binding constants decrease in the sequence acetohexamide > tolbutamide > chlorpropamide > carbutamide both for normal and glycated human serum albumins, with glycated giving lower values. These results provide a more quantitative picture of how these drugs bind with normal and modified human serum albumin and indicate capillary electrophoresis-frontal analysis to be another tool for examining the changes arising from modifications of albumin, or any other protein, with all its benefits like short analysis time, small sample requirement, and automation.
The adamantane moiety is the structural backbone of numerous compounds and its discovery launched a new field of chemistry studying the approaches to the synthesis as well as the physicochemical and biological properties of organic polyhedral compounds with practical application in the pharmaceutical industry. Adamantane derivatives have proven to be very potent compounds in a wide range of applications from systemic to topical therapy. This review summarizes the currently available adamantane derivatives in clinical practice (amantadine, memantine, rimantadine, tromantadine, adapalene, saxagliptin, vildagliptin), focusing on mechanisms of action, pharmacokinetics, pharmacodynamics and clinical trials. The adamantane-based compounds presented in this manuscript have been approved for a wide spectrum of indications (antivirals, antidiabetics and against Alzheimer's and Parkinson's disease). Each of the compounds proved to be of vital importance in their therapeutic indication for numerous patients worldwide. This review also considers the mechanisms of side effects to deliver a complete perspective on current treatment options.
- MeSH
- adamantan analogy a deriváty farmakokinetika terapeutické užití MeSH
- Alzheimerova nemoc farmakoterapie MeSH
- antivirové látky chemie farmakokinetika terapeutické užití MeSH
- chřipka lidská farmakoterapie MeSH
- diabetes mellitus 2. typu farmakoterapie MeSH
- hypoglykemika chemie farmakokinetika terapeutické užití MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The present study aimed to investigate the phytochemical profile of leaf methanol extracts of fourteen Smallanthus sonchifolius (yacon) landraces and their antioxidant, anticholinesterase and antidiabetic activities that could lead to the finding of more effective agents for the treatment and management of Alzheimer's disease and diabetes. For this purpose, antioxidant activity was assessed using different tests: ferric reducing ability power (FRAP), 2,2-diphenyl-1-picryl hydrazyl (DPPH), nitric oxide (˙NO) and superoxide (O2˙-) scavenging and lipid peroxidation inhibition assays. Anticholinesterase activity was investigated by quantifying the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities, whereas antidiabetic activity was investigated by α-amylase and α-glucosidase inhibition tests. To understand the contribution of metabolites, phytochemical screening was also performed by high performance liquid chromatography-diode array detector (HPLC-DAD) system. Among all, methanol extract of PER09, PER04 and ECU44 landraces exhibited the highest relative antioxidant capacity index (RACI). ECU44 was found to be rich in 4,5-di-O-caffeoylquinic acid (CQA) and 3,5-di-O-CQA and displayed a good α-amylase and α-glucosidase inhibition, showing the lowest IC50 values. Flavonoids, instead, seem to be involved in the AChE and BChE inhibition. The results of this study revealed that the bioactive compound content differences could be determinant for the medicinal properties of this plant especially for antioxidant and antidiabetic activities.
- MeSH
- alfa-amylasy antagonisté a inhibitory MeSH
- Alzheimerova nemoc farmakoterapie MeSH
- antioxidancia chemie farmakologie MeSH
- Asteraceae chemie MeSH
- cholinesterasové inhibitory chemie farmakologie MeSH
- diabetes mellitus farmakoterapie MeSH
- fenoly chemie MeSH
- flavonoidy chemie izolace a purifikace MeSH
- fytonutrienty aplikace a dávkování chemie MeSH
- hypoglykemika chemie farmakologie MeSH
- inhibitory glykosidových hydrolas chemie MeSH
- lidé MeSH
- listy rostlin chemie MeSH
- oxid dusnatý chemie metabolismus MeSH
- peroxidace lipidů účinky léků MeSH
- rostlinné extrakty aplikace a dávkování chemie MeSH
- vysokoúčinná kapalinová chromatografie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- analýza rozptylu MeSH
- diabetes mellitus 2. typu farmakoterapie metabolismus MeSH
- glukagonu podobný peptid 1 agonisté analogy a deriváty chemie škodlivé účinky terapeutické užití MeSH
- glykovaný hemoglobin metabolismus účinky léků MeSH
- hypoglykemie chemicky indukované MeSH
- hypoglykemika chemie škodlivé účinky terapeutické užití MeSH
- krevní glukóza metabolismus účinky léků MeSH
- lidé středního věku MeSH
- lidé MeSH
- multicentrické studie jako téma MeSH
- peptidy chemie škodlivé účinky terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- rozvrh dávkování léků MeSH
- výsledek terapie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- živočišné jedy chemie škodlivé účinky terapeutické užití MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
A simple, fast and sensitive HPLC method employing dual-channel coulometric detection for the determination of repaglinide in human plasma is presented. The assay involved extraction of repaglinide by ethyl acetate and isocratic reversed-phase liquid chromatography with dual-channel coulometric detection. The mobile phase composition was 50mM disodium hydrogen phosphate/acetonitrile (60:40, v/v), pH of the mobile phase 7.5 set up with phosphoric acid. For all analyses, the first cell working potential was +380mV, the second was +750mV (vs. Pd/H(2)). Calibration curve was linear over the concentration range of 5-500nmolL(-1). Rosiglitazone was used as an internal standard. The limit of detection (LOD) was established at 2.8nmolL(-1), and the lower limit of quantification (LLOQ) at 8.5nmolL(-1). The developed method was applied to human plasma samples spiked with repaglinide at therapeutical concentrations. It was confirmed that the method is suitable for pharmacokinetic studies or therapeutic monitoring.
- MeSH
- elektrochemické techniky metody MeSH
- hypoglykemika krev chemie MeSH
- karbamáty krev chemie MeSH
- kolorimetrie metody MeSH
- koncentrace vodíkových iontů MeSH
- lidé MeSH
- lineární modely MeSH
- piperidiny krev chemie MeSH
- reprodukovatelnost výsledků MeSH
- senzitivita a specificita MeSH
- thiazolidindiony analýza MeSH
- vysokoúčinná kapalinová chromatografie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Od prvního využití inzulinu ve 20. letech minulého století bylo technologickými změnami inzulinových přípravků dosaženo mnoha klinicky potřebných změn v působení inzulinu, zkrácení účinku, prodloužení účinku, snížení rizika hypoglykemií, příznivého vývoje hmotnosti. Tyto efekty byly dosaženy zejména záměnou inzulinu za inzulinová analoga. Vliv na kompenzaci diabetu a prevenci komplikací není dosahován jednotlivými přípravky, ale především kvalitou vedení léčby a spoluprací pacienta. Lékař by měl znát především klinické dopady změn struktury inzulinových přípravků tak, jak jsou uvedeny v jejich SPC. Potřebné prodloužení účinku je podobnými technologickými změnami dosahováno i u tzv. inkretinových mimetik.
A series of dinuclear copper(II) complexes involving 6-(benzylamino)purine derivatives, (HL(n)), as bridging ligands were synthesized, characterized and tested for both their in vitro and in vivo antioxidant activities. Based on results of elemental analyses, temperature dependence of magnetic susceptibility measurements, UV-vis, FTIR, EPR, NMR and MALDI-TOF mass spectroscopy, conductivity measurements and thermal analyses, the complexes with general compositions of [Cu(2)(mu-HL(n))(4)Cl(2)]Cl(2).2H(2)O (1-4) and [Cu(2)(mu-HL(n))(2)(mu-Cl)(2)Cl(2)] (5-7) were prepared {where n=1-4; HL(1)=6-[(2-methoxybenzyl)amino]purine, HL(2)=6-[(4-methoxybenzyl)amino]purine, HL(3)=6-[(2,3-dimethoxybenzyl)amino]purine and HL(4)=6-[(3,4-dimethoxybenzyl)amino]purine}. In the case of complexes 2, 3, 5 and 7, the antioxidant activities were studied by both in vitro {superoxide dismutase-mimic (SOD-mimic) activity} and in vivo {cytoprotective effect against the alloxan-induced diabetes (antidiabetic activity)} methods. The obtained IC(50) value of the SOD-mimic activity for the complex 5 (IC(50)=0.253 microM) was shown to be even better than that of the native bovine Cu,Zn-SOD enzyme (IC(50)=0.480 microM), used as a standard. As for the antidiabetic activity, the pretreatment of mice with complexes 3 and 7 led to the complete elimination of cytotoxic attack of alloxan and its free radical metabolites, used as a diabetogenic agent. The cytoprotective effect of these compounds was proved by the preservation of the initial blood glucose levels of the pretreated animals, as against the untreated control group.
- MeSH
- antioxidancia farmakologie chemická syntéza chemie MeSH
- cytoprotekce MeSH
- experimentální diabetes mellitus chemicky indukované MeSH
- financování organizované MeSH
- hypoglykemika farmakologie chemická syntéza chemie MeSH
- kinetin farmakologie chemická syntéza chemie MeSH
- měď chemie MeSH
- myši MeSH
- superoxiddismutasa metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
