A green catalyst WELPSA-catalyzed three-component condensation (Biginelli) process involving an aldehyde, barbituric/thiobarbituric/1,3-dimethylbarbituric acid, and urea/thiourea/guanidine hydrochloride in a single pot in presence of a green solvent for the production of DHPM have been presented. The catalyst is reusable and this methodology is scalable. By using the in vitro experiments, the antidiabetic potentiality of synthesized compounds that inhibit α-amylase along with α-glucosidase efficiencies was assessed. All the synthesized compounds except for 4a and 4e, showed the most significant inhibition for α-amylase and α-glucosidase activities. Among the synthesized DHPM compounds, 4c and 4b exhibited significant inhibition profiles compared to the standard antidiabetic drug acarbose. Furthermore, synthesized substances' energy-minimized structures, 3D structures, and DFT calculations were performed using Gaussian 09 software, hybrid models, and MM2 force approaches. Strong hydrogen bonds with amino acid residues Arg-672, Arg-600, Trp-613, Asp-404, Asp-282, and Asp-616 indicate that an α-glucosidase-inhibitory peptide may have hypoglycemic efficacy confirmed by the molecular docking study of the synthesized DHPM.

• Klíčová slova
• Biginelli, Green catalyst, Multicomponent, α-Amylase along with α-glucosidase,
• MeSH
• alfa-amylasy metabolismus   MeSH
• alfa-glukosidasy * metabolismus   MeSH
• barbituráty chemie   MeSH
• hypoglykemika farmakologie   chemie   MeSH
• inhibitory glykosidových hydrolas * chemie   MeSH
• katalýza MeSH
• simulace molekulového dockingu MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 1,3-dimethylbarbituric acid MeSH Prohlížeč
• alfa-amylasy MeSH
• alfa-glukosidasy * MeSH
• barbituráty MeSH
• hypoglykemika MeSH
• inhibitory glykosidových hydrolas * MeSH

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.

• Klíčová slova
• DNA, Psoralens, anti-inflammatory agents, antidiabetic, breast cancer, furocoumarins,
• 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
• Názvy látek
• analgetika MeSH
• antiinfekční látky MeSH
• antituberkulotika MeSH
• antitumorózní látky MeSH
• fikusin MeSH
• hypoglykemika MeSH
• neuroprotektivní látky 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.

• Klíčová slova
• Antidiabetic drug, Flow-gating interface, Hydrodynamic injection, Microdialysis, Sequence analysis, Short capillary separation,
• MeSH
• arginin MeSH
• biguanidy chemie   MeSH
• časové faktory MeSH
• draslík MeSH
• elektroforéza kapilární přístrojové vybavení   metody   MeSH
• hydrodynamika * MeSH
• hypoglykemika chemie   MeSH
• mikrodialýza MeSH
• pyruvaldehyd chemie   MeSH
• roztoky MeSH
• sodík MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• arginin MeSH
• biguanidy MeSH
• draslík MeSH
• hypoglykemika MeSH
• phenyl biguanide MeSH Prohlížeč
• pyruvaldehyd MeSH
• roztoky MeSH
• sodík 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.

• Klíčová slova
• Binding constant, Glycated human serum albumin, Human serum albumin, Sulfonylureas antidiabetics, capillary electrophoresis-frontal analysis,
• MeSH
• elektroforéza kapilární metody   MeSH
• glykosylace MeSH
• hypoglykemika chemie   MeSH
• lidé MeSH
• lidský sérový albumin chemie   MeSH
• sulfonylmočovinové sloučeniny chemie   MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• Názvy látek
• hypoglykemika MeSH
• lidský sérový albumin MeSH
• sulfonylmočovinové sloučeniny MeSH

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
• Názvy látek
• adamantan MeSH
• antivirové látky MeSH
• hypoglykemika MeSH

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
• Názvy látek
• bifázický inzulin MeSH
• dlouhodobě působící inzulin MeSH
• fixní kombinace léků MeSH
• glykovaný hemoglobin MeSH
• hemoglobin A1c protein, human MeSH Prohlížeč
• hypoglykemika MeSH
• insulin aspart, insulin aspart protamine drug combination 30:70 MeSH Prohlížeč
• insulin degludec, insulin aspart drug combination MeSH Prohlížeč
• inzulin aspart MeSH
• krevní glukóza MeSH
• NPH inzulin 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.

• Klíčová slova
• Smallanthus sonchifolius, anti-cholinesterase activity, anti-diabetic activity, antioxidant activity, phytochemical profile,
• 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
• Názvy látek
• alfa-amylasy MeSH
• antioxidancia MeSH
• cholinesterasové inhibitory MeSH
• fenoly MeSH
• flavonoidy MeSH
• fytonutrienty MeSH
• hypoglykemika MeSH
• inhibitory glykosidových hydrolas MeSH
• oxid dusnatý MeSH
• rostlinné extrakty MeSH

Fenugreek seeds are known for their characteristic smell of soup seasoning and as an ingredient of Indian curry. Traditionally the seeds are used as macerate for the treatment of diabetes, cough, and flatulence, to increase breast milk secretion, and for anti-inflammatory and aphrodisiac effects. The use is limited by its unpleasant smell and bitter taste which can be modified by adding mint leaves to the macerate. Antidiabetic properties are attributed mainly to galactomannan, 4-hydroxyisoleucin (4-OH-Ile), diosgenin and trigonelline. These substances demonstrate direct antidiabetic properties in clinical studies by increasing insulin secretion (4-OH-Ile), decreasing insulin resistance and glucose resorption from the GIT (galactomannan) and improvement in B-cells regeneration (trigonelline). Besides this main effect, the herb improves blood lipid spectre (4-OH-Ile, diosgenin), and has reno-protective (4-OH-Ile, trigonelline), neuroprotective (trigonelline) and antioxidant (diosgenin, trigonelline) effects. Antidiabetic efficacy of trigonelline is comparable to glibenclamide treatment and more effective than sitagliptine therapy. Given the large body of evidence and promising results in comparison with standard pharmacotherapy, fenugreek active substances have a potential to become a source of new antidiabetic medication.Key words: fenugreek Trigonella foenum-graecum diabetes mellitus type 2 biological activity.

• MeSH
• diabetes mellitus 2. typu farmakoterapie   MeSH
• fytoterapie metody   MeSH
• glibenklamid farmakologie   MeSH
• glukosa metabolismus   MeSH
• hypoglykemika chemie   izolace a purifikace   farmakologie   MeSH
• inzulin metabolismus   MeSH
• inzulinová rezistence MeSH
• lidé MeSH
• lipidy krev   MeSH
• sekrece inzulinu MeSH
• semena rostlinná MeSH
• Trigonella chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• srovnávací studie MeSH
• Názvy látek
• glibenklamid MeSH
• glukosa MeSH
• hypoglykemika MeSH
• inzulin MeSH
• lipidy 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
• rosiglitazon 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
• Názvy látek
• hypoglykemika MeSH
• karbamáty MeSH
• piperidiny MeSH
• repaglinide MeSH Prohlížeč
• rosiglitazon MeSH
• thiazolidindiony MeSH

Since the first application of insulin in the 1920s, many clinically necessary changes in the insulin action, effect reduction and extension, hypoglycemia risk reduction and positive weight development have been achieved by way of technological changes of insulin preparations. Such results have been achieved, in particular, by replacing insulin with insulin analogues. The impact on diabetes compensation and on the prevention of complications is not achieved by individual preparations but, in particular, by the quality of treatment and cooperation from the patient. The doctor should know, in particular, the clinical impacts of changes in the structure of insulin preparations as they are indicated in their respective SPCs. The necessary effect extension is achieved by similar technological changes, also with so-called incretin mimetics.

• MeSH
• hypoglykemika chemie   terapeutické užití   MeSH
• inzulin analogy a deriváty   chemie   terapeutické užití   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• hypoglykemika MeSH
• inzulin MeSH