Vol 50, No 1 (2016)
- Year: 2016
- Articles: 12
- URL: https://journals.rcsi.science/0091-150X/issue/view/15212
Molecular Biology Problems of Drug Design and Mechanism of Drug Action
Opioid κ Receptors as a Molecular Target for the Creation of a New Generation of Analgesic Drugs
Abstract
This review provides a brief description of the main structural and functional features of the κ opioid receptor, along with the properties of its agonists and the potential for using these in medicine. Of all the opioid receptor subtypes, κ receptors are the most attractive in terms of creating new drugs with a minimum of side effects. The opioid κ receptor is a member of the superfamily of metabotropic G-protein-coupled receptors. Opioid κ receptors are widely distributed in the CNS and at the periphery. They are involved in numerous physiological processes, including analgesia, regulation of neuroendocrine secretion, water balance, drinking and feeding behavior, autonomic functions, and the mechanisms of learning and memory. Data have been reported on the existence of three subtypes of κopioid receptor, though the molecular properties of only subtype 1 (ê1) have been studied.
Search for New Drugs
Synthesis and Antibacterial Activity of 3,6-Diaryl-7H-[1,2,4]Triazolo[3,4-b][1,3,4]Thiadiazines
Abstract
Interaction of 4-amino-5-(2-alkoxyphenyl)-4H-[1,2,4]triazole-3-thiols with substituted phenacyl bromides was used to synthesize 6-(2′-alkoxyphenyl)-3-aryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazines. Biological studies identified an interaction between chemical structure and antibacterial activity in this series of triazolothiadiazines.
Article
Synthesis and Antibacterial Activity of 3,4-Diaryl-5-(4-Guanidylsulfonylphenyl)-4,6-Dihydropyrrolo[3, 4-C]Pyrazol-6-Ones
Abstract
Interaction of 1,4,5-trisubstituted tetrahydropyrrol-2,3-diones with hydrazine hydrate was used to synthesize 3,4-diaryl5-(4-guanidylsulfonylphenyl)-4,6-dihydropyrrolo[3,4-c]pyrazol-6-ones. The antibacterial activity of these compounds was investigated.
Tropoxin – Drug for the Treatment of Migraine
Abstract
Anew antimigraine drug – Tropoxin (3-(3,4,5-trimethoxybenzoyloxyimino)-8-methyl-8-azabicyclo[1–3]octane hydrochloride) – was developed and was found to prevent or significantly weaken the constrictor reactions of cerebral arteries evoked by serotonin (5-HT) or the 5-HT2B/2C receptor agonist meta-chlorophenylpiperazine (m-CPP) in intact animals and in animals with ischemic brain damage. Tropoxin showed affinity for5-HT2 receptors in the brain and had antiaggregatory actions. It had no marked neurotropic properties and did not alter blood pressure responses to noradrenaline, acetylcholine, or histamine. Pilot clinical trials of Tropoxin provided evidence that it has high efficacy in the interictal treatment of frequent and severe migraine attacks.
Synthesis, Antimicrobial and Anticancer Evaluation of 2-Azetidinones Clubbed with Quinazolinone
Abstract
A novel series of 2-azetidinones clubbed with quinazolinone was synthesized using anthranilic acid. All the synthesized compounds were evaluated for their antimicrobial activity against two Gram positive bacterial strains (Bacillus subtilis and Staphylococcus aureus), one Gram negative bacterial strain (Escherichia coli) and two fungal strains (Candida albicans and Aspergillus niger). All the synthesized compounds were also screened for their anticancer activity against human breast cancer cell line, MCF-7. Results of antimicrobial and anticancer study indicate that compounds 12 and 5 (IC50 = 49.52 μM) are the most potent antimicrobial and anticancer agents, respectively.
Preparation and Molecular Composition of an Inclusion Complex of Dilsulfiram and Hydroxypropyl-β-Cyclodextrin
Abstract
An original method is proposed for preparing an inclusion complex based on disulfiram with hydroxypropyl-β-cyclodextrin for the treatment of cataract. Preparation of soluble product required a molar ratio of hydroxypropyl-β-cyclodextrin to disulfiram of at least 2:1, while the molar ratio of components in the inclusion complex was 1:1. Gel permeation chromatography was used to measure the mean hydrodynamic diameter of hydroxypropyl-β-cyclodextrin and inclusion complex molecules, and their molecular weights were calculated – which in both cases were 1.0 kDa. A scheme for the equilibrium of the inclusion complex is proposed.
Selection of Optimum Parameters for Separating Amino Acids in a Thin Layer of Sorbent
Abstract
A theoretical approach to selecting the optimal conditions for separating various amino acids in thin sorbent layers is demonstrated, i.e., the ability to predict Rf values from the equations for linear relationships when the polarity of the eluant is known. For simultaneous assays, the optimum values of Rf and the best separations are obtained by working with systems in the range 5.13 – 5.69 polarity units. The relationships found in the study can be used to develop various methods which, depending on the aims of the analysis and the suspected amino acid composition, will find use in quality control of formulations containing both single and multiple amino acids and fourth-generation vitamin complexes, as well as for separating and identifying free amino acids present in the raw materials for medicinal herbs and phytopreparations.
Effects of Molar Substitution on the Mobility of Hydroxyethylstarch Macromolecules in Solution
Abstract
The effects of molar substitution of hydroxyethylstarch on the macromolecule mobility in solution were studied by diffusion-ordered NMR spectroscopy (1H-DOSY) to measure mean self-diffusion coefficients of hydroxyethylstarch with different levels of modification of amylopectin. Molar substitution of hydroxyethylstarch had the opposite effect on macromolecule mobility from that of branching of the polymer chain. Standard samples and medicinal hydroxyethylstarch substances were shown to be nonuniform in terms of the degree of molar substitution. Inclusion of an additional parameter – molar substitution – into regression equations was found to increase the accuracy of measurement of the molecular weight of hydroxyethylstarches using analytical chemistry transport methods.
Medicinal Plants
Results of Experimental Studies of the Immunotropic Action of Polyprenols Extracted from Alcea Nudiflora
Abstract
Methods of extracting polyprenols from Alcea nudiflora and their immunotropic actions were studied. Administration of Alcea nudiflora polyprenols to mice simultaneously with immunization with sheep erythrocytes produced marked stimulation of primary antibody formation, apparent as an increase in the number of antibody-forming cells in the spleen. In addition, there were increases in the cellularity of the central and peripheral organs of immunity, along with increases in blood erythrocyte and leukocyte levels. The immunomodulatory action of Alcea nudiflora polyprenols was seen not only in normal animals, but also in animals with secondary immunodeficiency states developing in acute toxic hepatitis and sublethal irradiation. In terms of activity in these experiments, Alcea nudiflora polyprenols were as active as the known immunostimulatory substance Immunal.
Drug Synthesis Methods and Manufacturing Technology
Use of Membrane Filters in Production Technology for Sterile Drugs
Abstract
Filtration is one of the methods on which all the world’s chemical-pharmaceutical industries depend. This technological method is used for the sterilization of labile drugs and to provide them with the required properties. As a result of the introduction of strict GMP rules, most current plants use membrane filtration. We review here the main criteria used for selecting material for sterilizing filtration and provide examples of drugs whose manufacture uses this method.
Structure of Chemical Compounds, Methods of Analysis and Process Control
Characteristics of Assessments of the Sterility of Various Groups of Solid Drug Formulations for Parenteral Administration
Abstract
We present an information-analytical review of methods for evaluating the sterility of solid drug formulations. Current normative documentation regulating the quality of parenteral drugs is analyzed and the main limitations of the test method for this indicator are described. The probability of detecting microorganisms depending on the proportion of contaminated units in a batch and the quantity of sample taken for analysis is assessed. Results obtained from analysis of the State Register of Drugs relating to the nomenclature of drugs in solid formulations and their areas of use are presented. The characteristics of tests for individual pharmacological groups of drugs are described.