Volume 50, Nº 4 (2016)
- Ano: 2016
- Artigos: 13
- URL: https://journals.rcsi.science/0091-150X/issue/view/15215
Molecular Biology Problems of Drug Design and Mechanism of Drug Action
18F-FDG and Other Labeled Glucose Derivatives for Use in Radionuclide Diagnosis of Oncological Diseases (Review)
Resumo
This review addresses progress in the radionuclide diagnosis of oncological diseases using radiopharmaceutical preparations (RPP) based on labeled glucose derivatives. Most attention is paid to 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG), a glucose analog labeled with fluorine-18 (T1/2 = 110 min) and the only radiotracer for glycolysis, which is used in 90% of clinical studies using positron emission tomography (PET). We describe approaches to the synthesis of 18F-FDG and state-of-the-art automated technologies allowing tens of clinical doses of RPP for PET investigations of patients to be prepared. The main areas of use of PET with 18F-FDG in the diagnosis of various tumors are discussed, as is the potential for using glucose derivatives with other radionuclides (68Ga, 123I, 99mTc, 188Re) as tracers for use in PET and SPECT diagnosis.
Search for New Drugs
Synthesis and Anticonvulsive Activity of 5-Pyrrolidin-1-Ylpyrano[4″,3″:4′,5′]Pyrido-3′,2′:4,5]Thieno[3,2-D]Pyrimidine Derivatives
Resumo
A method for preparing the amino, alkoxy, and alkylsulfanyl derivatives of pyrano[4″,3″:4′,5′]pyrido-[3′,2′:4,5]thieno[3,2-d]pyrimidines based on 8-chloro-2,2-dimethyl-5-pyrrolidin-1-yl-1,4-dihydro-2H-pyrano[4″,3″:4′,5′]pyrido[3′,2′:4,5]thieno[3,2-d]pyrimidine was developed. The anticonvulsant activity of the compounds synthesized here was investigated.
Article
Synthesis and Analgesic Activity of N,6-diaryl-4-methyl-2-thioxo-1,2,3,6-tetrahydropyrimidine-5-carboxamides
Resumo
A three-component reaction of acetoacetanilides with a mixture of an aromatic aldehyde and thiourea was used to synthesize previously unknown N,6-diaryl-4-methyl-2-thioxo-1,2,3,6-tetrahydropyrimidine-5-carboxamides, which had high analgesic activity and low acute toxicity.
Synthesis, Structure, and Analgesic Properties of Phosphorylated Dihydro-1,4-Benzodiazepin-2-Ones*
Resumo
Condensation of 3-hydroxy-5-aryl-1.2-dihydro-3H-1.4-benzodiazepin-2-ones with diphenylchlorophosphine was found to produce 3- or 5-diphenylphosphine oxides with high analgesic activity; ED50 values were (0.08 ± 0.02) – (0.97 ± 0.27) mg/kg.
Synthesis and Cytotoxic Activity of (4-Substituted-benzylidene)-(3-Phenyl-1,2,4-Oxadiazol-5-YL)Methylamines
Resumo
This work was aimed at the synthesis and investigation of the cytotoxic activity of a series of Schiff bases having (4-substituted-benzylidene)-(3-phenyl-1,2,4-oxadiazol-5-yl)methylamine structure with different electronic natures of substituents in the phenyl ring. Thus, the study was intended to observe the effect of substituents with different electronic properties on the cytotoxic activity. The synthesized series of compounds (OP) were obtained by six-step synthesis with yields ranging from 12.23 to 25.77%. The chemical structures of these compounds were elucidated by H NMR. The cytotoxicity of compounds against human oral squamous cell carcinoma cell lines [Ca9-22 (gum), HSC-2 (mouth), HSC-3 (fluent), HSC-4 (language)] and human oral normal cells [HGF (gum fibroblasts), HPC (pulp cells), and HPLF (periodontal ligament fibroblasts)] was tested by MTT assay. Among the group of six OP compounds, bromo derivative OP2, non-substituted derivative OP1, and chloro derivative OP3 showed higher cytotoxicity (2.71-, 1.56-, and 1.53-fold, respectively) than the reference compound 5-FU. In addition, OP2 (3.27) exhibited the greatest selectivity index in this group. These compounds can be considered to be model structures for further studies.
Chemical Composition, Antioxidant and Antimicrobial Activities of Sanguisorba officinalis L. Extracts
Resumo
Sanquisorba officinalis has been used internally for the treatment of intestinal infections and duodenal ulcers, as well as hemorrhoids, phlebitis and varicose veins and female disorders, and topically to heal wounds, burns, and ulcers. In our study, the antioxidant and antimicrobial activities, as well as quantitative analysis of polyphenols (phenolic acids, flavonoids and total polyphenols) in methanol and aqueous extracts from S. officinalis herbs are presented. A correlation between the antioxidant activity and composition of tested extracts indicates that flavonoids are the major compounds causing scavenging of free radicals. Higher content of flavonoids was found in the methanol extract, while the content of total phenolics was higher in the aqueous extract. Both extracts from S. officinalis herbs showed antioxidant activity and high antimicrobial activity in a wide spectrum of test strains.
Studies of the Effects of Antibiotics on the Microflora of the Gastrointestinal Tract by Fluorimetry
Resumo
An approach to identifying the effects of different groups of antibiotics (tetracyclines, penicillins, cephalosporins) on the vital activity of lactobacilli by fluorimetry is described. The method is based on measurement of the fluorescence intensity of the intracellular metabolite nicotinamide adenine dinucleotide, reduced form (NADH). Different classes of antibiotics were found to have different effects on lactobacilli. Amoxycillin produced no microbial death, while tetracycline and cephazolin had different levels of fatal effects on lactobacilli.
Validation of a Method for Measuring the Molar Substitution of Hydroxyethylstarches by 1H NMR Spectroscopy
Resumo
Amethod for determining molar substitution of hydroxyethylstarches by 1H NMR spectroscopy was validated in terms of specificity, linearity, correctness, precision, and range of application. The method can be used to evaluate the parameter “molar substitution” in the framework of pharmacological expert assessment of hydroxyethylstarches as components of medicines.
Ultrafiltration-Based Extraction and HPLC Analysis of Naproxen Sodium in Human Plasma Samples: an Innovative Approach to Pharmaceutical Analysis
Resumo
The purpose of this study was to assess the possibility of using ultrafiltration-based extraction for pharmaceutical analysis and develop an innovative, rapid and simple analysis technique for determination of naproxen sodium in human plasma. The proposed extraction technique can be adapted for wide range of active pharmaceutical ingredients including water-soluble nonsteroidal anti-inflammatory drugs. Naproxen sodium was isolated from human plasma by ultrafiltration-based extraction and analyzed by HPLC. Proteins in the plasma samples were precipitated with methanol and the supernatant was filtered through commercial centrifugal filters (<3 kDa). The filtered part was vacuum centrifuged, dried, and then dissolved in water and centrifuged again. The supernatant was injected into the HPLC system where an ACE 5 μm C18 100 Å LC column (150 × 4.6 mm) was used. The mobile phase was acetonitrile – phosphate buffer (pH 3.0, 20 mM) 55 : 45 v/v mixture, the injection volume was 20 μL, and the UV detection was performed at 240 nm. Using the developed extraction technique combined with HPLC method, plasma samples containing naproxen sodium were successfully analyzed (RSD 1.04–6.47, bias 2.33–6.00).
Medicinal Plants
Effects of Bilberry Fruit and Shoot Extracts on Renal Excretory Function
Resumo
The diuretic and saluretic activities of aqueous and aqueous-alcoholic extracts of bilberry (Vaccinium myrtillus L.) fruits and shoots were studied in laboratory animals. The results obtained here showed that aqueous extracts of shoots and preparations based on fresh bilberry fruits had moderate diuretic and saluretic activities. Aqueous-alcoholic extracts of air-dried fruits and shoots decreased diuresis and saluresis as compared with a control group.
Drug Synthesis Methods and Manufacturing Technology
Preparation of Biologically Active Film-Forming Materials Based on Polyphosphate-Modified Chitosan
Resumo
The processes of preparing film-forming materials based on chitosan with surface modification and ionic cross-linking using sodium tripolyphosphate and potassium pyrophosphate respectively were studied. Optimum cross-linking conditions were identified by studying the interactions of chitosan with different levels of amino group protonation with polyphosphates with different numbers of ionized groups. These studies showed that changes in the duration of treatment of films allowed the level of swelling to be varied over the range 165% to 148% for potassium pyrophosphate and from 196% to 80% for sodium tripolyphosphate. Studies of the kinetics of study drug release showed that changes in the conditions used for modification with polyphosphates could increase the duration of release of the biologically active components to 8 h.
Structure of Chemical Compounds, Methods of Analysis and Process Control
Pharmacopeia Standard Samples and Their Practical Application in the National Drug Standardization System
Resumo
Standard samples constitute one of the key elements in the medicines standardization system. In pharmacopeia analysis in the Russian Federation and many foreign countries, the use of standard samples is regulated by the corresponding normative documents and pharmacopeia monographs. There are different classifications for standard samples and, depending on purpose, certification programs. Standard samples used in compliance with the requirements of pharmacopeia articles or monographs in international, regional and national pharmacopeias are generally termed pharmacopeia standard samples.