Xanthines
They have diverse biological activities, including stimulant, diuretic, and bronchodilator effects.
Xanthines are commonly used in the treatment of respiratory conditions, such as asthma and chronic obstructive pulmonary disease (COPD), as well as in the management of certain cardiovascular disorders.
Research into the therapeutic potential of xanthines is an active area of investigation, with ongoing studies exploring their effeects on cognition, neuroprotection, and other physiological processes.
This MeSH term provides a concise overview of the key characteristics and pharmacological applications of this improtant class of compounds.
Most cited protocols related to «Xanthines»
The Protein Data Bank (PDB) provides several receptor-ligand complex alternatives for Chk1. However, the structure of this receptor complexed with caffeine is not available in the PDB, which makes it necessary to select the receptor-ligand complex (for further docking) as described below:
Selection of the receptor-ligand complex Chk1 (target protein) was performed taking into account (1) the structural similarity (visual inspection) of the ligands to the xanthine scaffold structure, regarding the presence of the heterocyclic rings; followed by (2) the overlap of the ligands with the caffeine structure, in relation to the overlap similarity values.
For PDB selection, only small ligand structures (characteristic common to the molecules here studied) from target in complex with only one ligand were selected. The structural similarity was accessed in the Discovery Studio 4.0 Client tool [24 ]. The ligands obtained were analyzed regarding the overlap similarity with caffeine.
The training set molecules used for the construction of the pharmacophore model were selected in decreasing biological activity sequence (from 0.01 to 0.24 mM), containing the most active, since the activity is a critical factor for the determination of the pharmacophore characteristics and for the validation of the model Multiple Linear Regression (MLR) [11 , 12 (link)]. Caffeine and xanthine molecules were introduced in the training set, according to the following considerations: (1) introduction of caffeine, here used as the reference/prototype molecule; (2) introduction of xanthine, because it has the active scaffold of the molecules here investigated. A total of 21 molecules comprise of the final training set.
The test set comprised 9 molecules randomly selected, which was here used for external validation of the MLR model. Structures were drawn using the ChemScketch software [13 ] and saved in the mol format, except caffeine, for which the crystallographic pose was retrieved from the Cambridge Structural Database portal at
converted to mol2 using the Open Babel tool 2.3.2 [14 ]. The geometries of the molecules were optimized according to the Molecular Mechanics MM+ Force Field, using the HyperChem 7 program [15 ].
Most recents protocols related to «Xanthines»
Example 1
The present example described the preparation of an HMG glucoside for use in a flavor composition through the hydrolysis of cocoa bean liquor made from West African cocoa beans.
Reagents: A solution of 4N HCl was prepared by adding 100 mL 34-37% HCl in a 250 mL volumetric flask and filling it with water. A solution of 4N NaOH was prepared by dissolving 80 g NaOH pellets in 500 mL of water in a volumetric flask.
Method: Cocoa liquor was run through a sieve and 30.09 g of fine powder was weighed into a 500 mL 3-neck round-bottom flask. The liquor was dissolved in 4N HCl (200 mL) and a stir bar was added to the flask. The sample was stirred at room temperature until the liquor was fully dispersed and flowed freely. A condenser was affixed to the flask and held at 8° C. A digital thermometer was pierced through a rubber stopper to measure the temperature of the solution. The third neck was plugged with a rubber stopper. The flask was wrapped in aluminum foil and heated to approximately 106° C. using a heating mantle. The sample was refluxed for 4.5 hours and left to cool to room temperature. The sample was transferred to a 1 L beaker and neutralized to pH 7 with 4N NaOH using a digital pH meter (pH 6.98 @29° C.). The sample was divided equally into 4 250 mL centrifuge tubes and centrifuged for 10 minutes @ 4500 rpm. The supernatant was filtered under vacuum through a Buchner funnel. The filtrate was then transferred to 2 32 oz plastic containers and lyophilized (yield 52.50 g).
1. Hydrolysis of Cocoa Powder
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- Preparation: A solution of 4N HCl was prepared by adding 100 mL 34-37% HCl in a 250 mL volumetric flask and filling it to the line with water. A solution of 4N NaOH was prepared by dissolving 80 g NaOH pellets in 500 mL of water in a volumetric flask.
- Procedure: Cocoa liquor made from Theobroma cacao cocoa beans was run through a sieve and 30.09 g of fine powder was weighed into a 500 mL 3-neck round-bottom flask. The liquor was dissolved in 4N HCl (200 mL) and a stir bar was added to the flask. The sample was stirred at room temperature until the liquor was fully dispersed and flowed freely. A condenser was affixed to the flask and held at 8° C. A digital thermometer was pierced through a rubber stopper to measure the temperature of the solution. The third neck was plugged with a rubber stopper. The flask was wrapped in aluminum foil and heated to approximately 106° C. using a heating mantle. The sample was refluxed for 4.5 hours and left to cool to room temperature. The sample was transferred to a 1 L beaker and neutralized to pH 7 with 4N NaOH using a digital pH meter (pH 6.98 @ 29° C.). The sample was divided equally into 4 250 mL centrifuge tubes and centrifuged for 10 minutes @ 4500 rpm. The supernatant was filtered under vacuum through a Buchner funnel. The filtrate was then transferred to 2 32 oz plastic containers and lyophilized.
2. Ethanol Extraction of Hydrolyzed Cocoa Powder
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- The hydrolyzed cocoa powder was extracted with ethanol to remove a bulk of the salts generated during neutralization. Hydrolyzed cocoa powder (50.36 g) was divided equally into 2 500 mL centrifuge tubes. Ethanol (200 mL) was added slowly to each tube as to not disturb the sample. The samples were shaken for 15 minutes on an autoshaker and then centrifuged for 10 minutes @4500 rpm. The supernatant was decanted into a 1000 mL round-bottom flask. The residue was scraped off the bottom of the tubes and redissolved in ethanol (200 mL each). The samples were shaken for 15 minutes on an autoshaker and then centrifuged for 10 minutes @ 4500 rpm. The supernatant was combined with the previous supernatant and evaporated under reduced pressure to remove all organic solvent. The remaining solids were redissolved in approximately 100 mL deionized water and lyophilized.
3. SPE (Solid Phase Extraction) Fractionation of HCP (Hydrolysed Cocoa Powder) Ethanol Extract
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- The extract previously obtained was further fractionated to exhaustively remove the salts and hydrophilic molecules. HCP ethanol extract was transferred to 14 glass vials (approximately 0.5 g each, 20 mL volume) and dissolved in DI water (10 mL). The samples were shaken until dissolved (approximately 1 minute). The samples were filtered through a syringe and PTFE filter to remove particulates as necessary. A solid phase extraction (SPE) cartridge (20 g/60 mL, C18 stationary phase) was conditioned sequentially with DI water (100 mL), methanol (100 mL), and DI water (100 mL). The sample (10 mL) was then loaded onto cartridge and washed with DI water (100 mL) and extracted with methanol (100 mL). The cartridge was reconditioned and the remaining 13 samples were washed and extracted as previously described. The organic solutions were combined and rotary evaporated under reduced pressure. The residue was redissolved in DI water and lyophilized using a Labconco freeze dryer. The sample was separated by high-performance liquid chromatography (HPLC) to narrow down the taste-active molecules of interest.
1. Liquid/Solid Extraction of Liquor
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- Cocoa Liquor made from cocoa beans sourced from Papua New Guinea (PNG liquor) (600 g) was frozen in liquid nitrogen and ground into a fine powder with a laboratory mill. The powder was divided equally into six plastic centrifuge tubes (500 mL volume). Each sample (100 g PNG liquor) was extracted with diethyl ether (200 mL) for 15 minutes using an autoshaker to remove the fat. After centrifugation (10 min, 4500 rpm), the supernatant was discarded. The extraction process was repeated three more times for a total of four times. The remaining defatted liquor was left to air dry in a fume hood overnight. Defatted liquor (200 g) was divided equally between four plastic centrifuge bottles (250 mL volume). To each sample (50 g defatted PNG liquor), 150 mL 70:30 acetone:water was added. The bottles were placed on an autoshaker for 15 minutes. Each sample was centrifuged (5 min, 3500 rpm) and then the supernatant was vacuum filtered using Whatman 540 filter paper and a Buchner funnel. The residue was freed from the bottom of the bottles by hand and additional 70:30 acetone:water (100 mL) was added to each sample. The samples were shaken for 15 minutes using an auto-shaker. After centrifugation (10 min, 4500 rpm), the supernatant was vacuum filtered again using the same procedure described above. The supernatants from each extraction were combined (˜800 mL) and the residue was discarded. The supernatant was rotary evaporated under reduced pressure and the remaining aqueous solution (˜250 mL) was transferred into a separatory funnel (1000 mL volume). The aqueous solution was washed with Dichloromethane (3×300 mL) to remove any xanthines. The dichloromethane layer was discarded, then the aqueous solution was washed sequentially with n-butyl acetate (3×300 mL), ethyl acetate (3×300 mL), and methyl acetate (3×300 mL) to remove procyanidins. The organic layers were discarded and the aqueous solution (F7) was rotary evaporated under reduced pressure to remove any remaining solvent. The remaining water solution was lyophilized using a Labconco freeze dryer (100×103 mbar, −40° C.). Sensory analysis was performed and the savory attribute was found to be in F7.
2. Solid Phase Extraction (SPE)
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- For removal of any residual salts, treated PNG liquor powder (F7) was transferred to 14 glass vials (20 mL volume, approximately 0.5 g sample in each vial) and dissolved in DI water (10 mL). The samples were shaken until dissolved (approximately 1 minute). A solid phase extraction (SPE) cartridge (20 g/60 mL, C18 stationary phase) was conditioned sequentially with DI water (100 mL), methanol (100 mL), and DI water (100 mL). The vacuum was broken and the sample (10 mL) was then loaded onto cartridge. The vacuum was resumed and the sample was washed with DI water (100 mL). The receptacle flask was changed and the sample was extracted with methanol (100 mL). The cartridge was reconditioned and the remaining 13 samples were washed and extracted as previously described. The organic solutions were combined and rotary evaporated under reduced pressure. The residue was redissolved in DI water and lyophilized using a Labconco freeze dryer (100×103 mbar, −40° C.). Sensory analysis confirmed the presence of the savory attribute in the organic fraction.
To establish levels of methylone, MDMA and their metabolites, blood and oral fluid samples were collected at baseline and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, and 24 h after administration. Urine samples were collected at various time points throughout the session until 24 h (0–4 h, 4–8 h, 8–12 h, 12–24 h). Data on methylone and MDMA concentrations from this study are not presented, although the pharmacokinetics of methylone at doses ranging from 50 to 200 mg from pilot studies have been published (see study design) (Poyatos et al., 2022a (link)).
Total fees for all services received were converted from Tanzanian shilling to US dollars using the World Bank official exchange rate average for 2018 (2,263.78 TZS = 1.00 USD). Where available, a breakdown of separate fees paid for consultation with the clinician, lab tests and drugs is reported.
Standardised patient (SP) case presentation and correct management
Case | Initial presentation | Further details given if probed | Required drugs and tests | Palliative drugs¹ | Appropriate tests² |
---|---|---|---|---|---|
Asthma | “I have had a problem with breathing, and last night it became terrible” | Shortness of breath when moving furniture/cleaning. Wheezing and non-productive cough throughout attack. Attacks at night for a year with increasing frequency and severity. Attacks brought on by cleaning or physical activity. Had coughing fits as a child, and a sibling with a similar problem. | Prescription of salbutamol or other beta-2 antagonist or steroid inhaler. | Other \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${ \beta }_{2}$$\end{document} | Allergy tests, ECG, HIV, X-ray. |
TB | “I have had a cough that is not getting better” | Productive cough for three weeks, one week course of amoxicillin without improvement. Low grade fevers, chest pain, loss of appetite, weight loss, night sweats. | Order or refer for sputum TB testing (including referral to a higher-level public health facility which could test for TB, even if testing was not mentioned). | Cold and flu combinations, cough syrups, NSAIDs and paracetamol. | Complete blood count, HIV, malaria, X-ray, Widal. |
¹Drugs which are suitable for managing symptoms associated with the condition, and therefore not classified as unnecessary
²Tests which may give the provider useful information in planning management of the patient
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More about "Xanthines"
These compounds have diverse biological activities, including stimulant, diuretic, and bronchodilator effects.
Xanthines are commonly used in the treatment of respiratory conditions like asthma and COPD, as well as in the management of certain cardiovascular disorders.
Theophylline and caffeine are two well-known xanthine derivatives.
Theophylline is a bronchodilator used to treat asthma and COPD, while caffeine is a stimulant found in coffee, tea, and chocolate.
Theobromine, another xanthine compound, is found in cocoa and has diuretic and vasodilatory properties.
Researchers are actively investigating the therapeutic potential of xanthines, exploring their effects on cognition, neuroprotection, and other physiological processes.
These studies involve various experimental methods, such as cell culture, animal models, and clinical trials.
To optimize your xanthines research, consider using tools like PubCompare.ai, which can help you efficiently locate the best protocols from literature, preprints, and patents, and compare them to identify the most reproducible and effective methods.
This can unlock new insights and accelerate your research.
Additionally, common laboratory techniques used in xanthines research may include the use of FBS, penicillin/streptomycin/L-glutamine, BTX ECM 630 machine, acetonitrile, and dexamethasone.
Forskolin, a plant-derived compound, has also been studied for its potential therapeutic effects related to xanthines.
By incorporating these insights and related terms, you can create a comprehensive and SEO-optimized block of text that provides a clear and informative overview of the fascinating world of xanthines and their applications.