Том 53, № 4 (2019)
- Жылы: 2019
- Мақалалар: 15
- URL: https://journals.rcsi.science/0091-150X/issue/view/15305
Article
Conjugates of Prostate-Specific Membrane Antigen Ligands with Antitumor Drugs
Аннотация
Conjugates for targeted delivery that are based on low-molecular-mass prostate specific membrane antigen (PSMA) inhibitors are widely used and developed because of the deficiencies of existing methods for treating and diagnosing prostate cancer. The major classes of low-molecular-mass PSMA inhibitors, drug classes, and their mechanisms of action are discussed. Therapeutic conjugates for targeted delivery that are based on them are analyzed. Structural features of the linker that affect the biological activity and selectivity are identified.
Insulin Preparation for Blood Glucose-Level Regulation
Аннотация
A new approach for delivering insulin into the bloodstream through the gastrointestinal system after peroral administration of diluted insulin solutions to animals with experimental diabetes was studied. It was shown that such solutions provided a physiological pathway for delivering insulin into the bloodstream.
Biological Surveying of Diverse Schiff Base Compounds: Antiproliferative, Antiradical and Enzyme Inhibition Activity
Аннотация
Schiff base compounds (((1Z,1′Z)-(((ethane-1,2-diylbis(sulfanediyl))bis(2,1-phenylene))bis(azanylylidene)) bis(methanylylidene)) bis(4,1-phenylene))diboronic acid (1), 1,1′-((1Z,1′Z)-([1,1′-biphenyl]-4,4′-diylbis( azanylylidene)) bis(methanylylidene)) bis(naphthalen-2-ol) (2), 4,4′-((1Z,1′Z)-([1,1′-biphenyl]-4,4′-diylbis(azanylylidene)) bis(methanylylidene)) bis(2-methoxy phenol) (3), (N4Z,N4′Z)-N4,N4′-bis(4-(dimethyl amino) benzylidene)-[1,1′-biphenyl]-4,4′-diamine (4), (E)-2-((2-hydroxybenzylidene)amino) terephthalic acid (5), and (E)-2-(((2-hydroxynaphthalen-1-yl)methylene)amino)terephthalic acid (6) have been synthesized. The structural identification was confirmed by spectroscopic techniques. The antiproliferative, antiradical, and enzyme activities were investigated in biological experimen0ts. The obtained results showed that Schiff base compounds 1 – 6 exhibited meaningful features in various biological tests. A comparison of compound 1 (containing boron atom in the structure) to compounds 2 – 6 shows that the inclusion of boron in the Schiff base determines whether this would increase or not the efficiency in biological experiments. Hereby, compound 1 exhibited significantly different results in all applications.
Antiviral Properties of the New Coordination Compound Silver Bis(Citrato)Germanate
Аннотация
The new coordination polymer silver bis(citrato)germanate was synthesized and exhibited pronounced antiviral activity against human influenza virus strains A/Hong Kong/1/68 (H3N2) and A/Puerto Rico/34 (H1N1). Its effective dose was five times lower than that of the reference drug oseltamivir, which made this compound promising for further studies in animal models.
Design and Synthesis of 2-Substitutedphenyl Benzo[D]Thiazole Derivatives and Their β-Amyloid Aggregation and Cholinesterase Inhibitory Activities
Аннотация
The occurrence of amyloid-β (Aβ) and reduced cholinergic tranmission are two major hallmarks of Alzheimer’s disease (AD). Therefore, a series of new 2-phenylbenzo[d]thiazoles substituted with azole/piperazine moieties were designed, synthesized, and evaluated as potential dual inhibitors of Aβ aggregation and cholinesterase (ChE) activities. In vitro studies showed that compound 2m containing an imidazole ring strongly inhibited Aβ1–40 (49.2%) and Aβ1-42 aggregation (60.6%). All derivatives exhibited weak inhibitory activities against both acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Therefore, compound 2m may represent promising therapeutic option for inhibiting Aβ-mediated pathology in AD.
Silica Nanoparticles: Preparation, Characterization and Applications in Biomedicine
Аннотация
A rapid and effective methodology has been developed in order to obtain silica nanoparticles which are broadly characterized by various techniques including electron microscopy, differential scanning calorimetry, ultraviolet and infrared spectroscopy, determining their charge via electrophoretic mobility, and zeta potential measurements. The ability of nanoparticles to incorporate distinct active ingredients, 5-fluoruracil and two UV protectors (Neo Heliopan BB and Eusolex 232), has been studied in order to verify (among other parameters) the effectiveness of their encapsulation and the most appropriate conditions for carrying out this process. The obtained nanoparticles were found to have an ideal size for administration via different means and a zeta potential that indicated their good stability.
Subvisible Particulate Matter in Therapeutic Protein Injections
Аннотация
Strategies for determining particulate matter in therapeutic protein injections, including extrinsic and intrinsic particles, are reviewed. Special attention is devoted to the advantages and limitations of various methods used for these purposes, each of which enables different particle characteristics to be determined. The source of particles (extrinsic, intrinsic, or inherent) can be understood better and particle-size distribution and other characteristics can be studied and used to differentiate them if methods based on different measurement principles are used. Protein aggregates in drugs have broad particle-size distributions, from oligomers to particles reaching hundreds of microns. The particle properties can be used to assess the risk associated with protein aggregates in the drug and to study their possible formation mechanisms. Such information could be useful during drug development and manufacturing to reduce the particulate matter content.
Development of a Technique for Codetermination of Tannin and Gallic Acid in Medicinal Plant Raw Material
Аннотация
Development and validation of a new technique for direct spectrophotometric quantitative determination of high- and low-molecular-mass tannins are reported. The proposed method enables simultaneous codetermination using Firordt calculations of tannins and gallic acid in medicinal plant raw material and herbal preparations without preliminary separation from complicated mixtures with other biologically active compounds found in the plant extracts. The developed method was validated (using nettle raw material as an example). The contents of gallic acid and tannins in the samples were (1.20 ± 0.04)% and (1.52 ± 0.03)%, respectively, which agreed with literature data.
Study of Dolutegravir Degradation and Spectroscopic Identification of Products by LCMS, 1H and 13C NMR Techniques
Аннотация
Stability study for dolutegravir bulk drug was performed and the degradation products formed were identified by chromatography (HPLC, LCMS) and spectroscopy (ESI-MS, FTIR, 1H and 13C NMR) techniques. Degradation of the drug in acidic and peroxide environment yielded one common major degradant f ((2,4-difluorophenyl) methanamine) with a mass peak at m/z = 182.44. In addition to this, five more minor degradation products (a, b, c, d and e) were formed. The structure interpretation showed that the drug degraded to its synthetic precursor and no extra structures were formed. Hence, it was suggested that drug dolutegravir should be kept away from acidic and oxygen rich conditions.
Development and Validation of a Stability-Indicating Ion-Pair RP-HPLC Method for Determination of Bethanechol with UV Detection: Application to Pharmaceutical Analysis
Аннотация
A rapid and stability indicating ion-pair RP-HPLC method was developed for estimation of bethanechol chloride (BC) in pharmaceutical preparations. The separation was achieved on a phenyl column using a mobile phase consisting of 0.05 M phosphate buffer (pH 6) – ethanol (98:2 v/v) mixture containing 0.56 mg/mL of sodium 1-heptanesulfonate. Quantitation was achieved with UV detection at 190 nm. In forced degradation studies, the drug was subjected to oxidation, hydrolysis, photolysis, and heat. The method was validated for specificity, selectivity, linearity, precision, accuracy, and robustness. The analytical procedure was found to be linear in a BC concentration range of 5.0 – 500.0 μg/mL (r2 = 0.9997). Precision was evaluated by replicate analysis in which%deviations from relative standard values of peak areas were found below 2.0. The recoveries obtained (99.0 – 102.0%) ensure the accuracy of the proposed method. Impurities as well as excipients were well resolved from the parent drug. Accordingly, the proposed validated procedure was proved to be suitable for routine and stability analysis of BC in pharmaceutical preparations.
Molecular-Biological Problems of Drug Design and Mechanism of Drug Action
Practical Issues of Preclinical Pharmacokinetic Investigations of New Drugs (Review)
Аннотация
Several issues with pharmacokinetic studies of new drugs, in particular, experiment planning, development of study protocols, dose selection, and administration routes, are reviewed. The number of used animals is justified statistically with respect to bioethics. The pharmacokinetic study protocol is discussed in more detail according to domestic regulatory requirements. Modern approaches to combining bioanalytical methods with pharmacokinetic studies are described.
Search for New Drugs
Water-Soluble Anionic C60-Fullerene Derivatives as Antidotes for HG(II) Ions in Tests on Escherichia Coli Cells
Аннотация
Three water-soluble C60-fullerene derivatives functionalized by anionic adducts of various chemical compositions and structures were prepared in highly specific reactions of chlorofullerene C60Cl6. Hybrid metal-organic complexes formed and aggregated in several instances in aqueous solution in the presence of stoichiometric (1:1 by moles) amounts of synthesized C60-fullerene derivatives and Hg(II) ions. The bioavailability of Hg(II) ions for Escherichia coli cells was reduced by such a reaction and manifested as decreased toxicity for strain E. coli K12 TG1 pF1 or weakened protective reactions of strain E. coli K12 MG1655 pMerA'::lux. The most pronounced protective effect was recorded for the C60-fullerene derivative functionalized by S-containing adducts of general formula –S(CH2)10CO2K with antidote activity comparable with that of the pharmacopoeial preparation Unithiol.
Medicinal Plants
Sorption Properties of Sunflower Husk Melanins
Аннотация
The sorption properties of sunflower husk melanins were studied according to pharmacopoeial monograph GPM.1.2.3.0021.15 using marker compounds methylene blue, methyl orange, gelatin, and iodine. The sorption capacities of the studied samples were found to be 190.9 ± 4.2 mg/g for methylene blue; 302.1 ± 1.8, methyl orange; 114.7 ± 2.8, gelatin; and 38.4 ± 2.4%, I2 . The sorption capacities of the samples were greater than those of the sorbents Polifepan and Polysorb and comparable with that of activated charcoal for medium-molecular-mass toxicants. The melanins showed high affinity for anionic substances. The protein-binding capacities of the melanins were inferior only to that of Polysorb and significantly greater than those of Polifepan and activated charcoal. The sorption capacity for I2 matched that of Polifepan and was >1.5 times less than that of activated charcoal. The results showed that enterosorbents based on melanins could be developed.
Drug Synthesis Methods and Manufacturing Technology
Development and Study of Anxiolytic Effect of Gml-1 Tablet Dosage Form
Аннотация
Novel pyrrolo[1,2-a]pyrazine ligands of 18-kDa translocator protein (TSPO) were synthesized at Zakusov Research Institute of Pharmacology. Pharmacological studies of drug substance N-benzyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-1) were consistent with high affinity for TSPO and significant anxiolytic activity. A finished dosage form of GML-1 drug substance was developed and exhibited pronounced anxiolytic activity after intragastric administration over a wide dose range.
Structure of Chemical Compounds, Methods of Analysis and Process Control
Using a Molecular Sensor Array with Colorimetric Detection to Identify Active Ingredients in Drug Formulations
Аннотация
A method for multiplex digital colorimetric qualitative analysis of nonsteroidal anti-inflammatory drugs (meloxicam, acetylsalicylic acid and its metabolites, paracetamol), β-adrenoblockers (carvedilol), secretolytics (bromhexine), fluoroquinolones (ofloxacin), metabolic stimulants (meldonium dihydrate), etc., was developed. The molecular chip operating efficiency was confirmed by verifying the authenticity of >40 medicinal substances. The proposed universal approach was new in principle and could be used for pharmaceutical quality control.