Influence of protonation on the geometry of 2-{[(2,6-dimethylphenoxy)ethyl]amino}-1-phenylethan-1-ol: crystal structures of the free base and of its chloride and 3-hydroxybenzoate salt forms

The aroxyalkylaminoalcohol derivatives are a group of compounds known for their pharmacological action. The crystal structures of four new xylenoxyaminoalcohol derivatives having anticonvulsant activity are reported, namely, 2-{[2-(2,6-dimethylphenoxy)ethyl]amino}-1-phenylethan-1-ol, C18H23NO2, 1, the salt N-[2-(2,6-dimethylphenoxy)ethyl]-1-hydroxy-1-phenylethan-2-aminium 3-hydroxybenzoate, C18H24NO2 +·C7H5O3 −, 2, and two polymorphs of the salt (R)-N-[2-(2,6-dimethylphenoxy)ethyl]-1-hydroxy-1-phenylethan-2-aminium chloride, C18H24NO2 +·Cl−, 3 and 3p. Both polymorphs crystallize in the space group P21212 and each has two cations and two anions in the asymmetric unit (Z′ = 2). The molecules in the polymorphs show differences in their molecular conformations and intermolecular interactions. The crystal packing of neutral 1 is dominated by intermolecular O—H...N hydrogen bonds, resulting in the formation of one-dimensional chains. In the crystal structures of the salt forms (2, 3 and 3p), each protonated N atom is engaged in a charge-assisted hydrogen bond with the corresponding anion. The protonation of the N atom also influences the conformation of the molecular linker between the two aromatic rings and changes the orientation of the rings. The crystal packing of the salt forms is dominated by intermolecular O—H...O hydrogen bonds, resulting in the creation of chains and rings. Structural studies have been enriched by the calculation of Hirshfeld surfaces and the corresponding fingerprint plots.

Beyond Lipid-Lowering: Effects of Statins on Cardiovascular and Cerebrovascular Diseases and Cancer

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are administered as first-line therapy for hypercholesterolemia, both as primary and secondary prevention. Besides the lipid-lowering effect, statins have been suggested to inhibit the development of cardiovascular disease through anti-inflammatory, antioxidant, vascular endothelial function-improving, plaque-stabilizing, and platelet aggregation-inhibiting effects. The preventive effect of statins on atherothrombotic stroke has been well established, but statins can influence other cerebrovascular diseases. This suggests that statins have many neuroprotective effects in addition to lowering cholesterol. Furthermore, research suggests that statins cause pro-apoptotic, growth-inhibitory, and pro-differentiation effects in various malignancies. Preclinical and clinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. The pleiotropic effects of statins on cardiovascular and cerebrovascular diseases have been well established; however, the effects of statins on cancer patients have not been fully elucidated and are still controversial. This review discusses the recent evidence on the effects of statins on cardiovascular and cerebrovascular diseases and cancer. Additionally, this study describes the pharmacological action of statins, focusing on the aspect of ‘beyond lipid-lowering.’

Formulation and evaluation of dexlansoprazole extended-release tablet

Dexlansoprazole (DSP) is a proton pump inhibitor, it used to treat GERD and ulcer colitis. DSP works by decreasing the volume of acid in the stomach. DSP is an acid-labile medication that may be destroyed in the stomach's acidic pH. A coating technique was used to postpone drug release in the stomach, which can extend pharmacological activity. Shellac can be used to develop the sustain release tablet of dexlansoprazole as retardation of the drug (dexlansoprazole) was observed in the acidic pH of the stomach, and hence a sustain coated dexlansoprazole tablet was prepared and evaluated. The coating's primary function is to allow for the delayed, immediate, and prolonged delayed release of DSP. DSP coating with different polymers inhibits faster degradation in the acidic pH of the stomach, therefore increasing pharmacological action. DSP coating with different polymers inhibits fast degradation in the stomach's acidic pH, enhancing pharmacological action. The major function of the coating is to enable for the delayed, immediate, and prolonged delayed release of DSP. DSP coating with different polymers inhibits fast breakdown in the stomach's acidic pH, enhancing pharmacological action.

β- sitosterol in Various Pathological Conditions: An Update

Phytosteroids are biologically active compounds found naturally in herb plasma membranes, with a chemical composition similar to animal plasma membrane cholesterol. It can be found in almost all fats abundant plant’s diets. One of the vital phytosterols is β-sitosterol which has several biological activities. It has been proved in various in-vivo and in-vitro research in which β-sitosterol stabilized several physiological activities like as antioxidant, CNS activity (like anti-alzheimer, anxiolytic and sedative effects, CNS depressant activity), lipid-lowering effects (like nonalcoholic fatty liver disease), antidiabetic, anti-inflammatory and analgesic effects, anticancer and immunomodulatory, protective effects in pulmonary fibrosis, wound healing effects and anti-viral and COVID-19 activity. The experimental research on β-sitosterol shows that it can be used as a nutritional supplement to combat various existing diseases. In this review, we are highlighting the most significant pharmacological action of β-sitosterol on the basis of available literature.

Pharmacological action and physiological effect of the venom of the honey bee Apis mellifera Caucasica

The present’s experimental data on the influence of the venom of the honey bee on the life span of experimental animals irradiated with small doses of gamma radiation on physiological and pharmacological action venom of the honey bee Apis mellifera Caucasica. The aim of the studies was to study the radioprotective effect of the pre-introduced venom Apis mellifera Caucasica with a single gamma irradiation of 60Co mice at doses of 1.3, 5, 7, 10 Gy at irradiation dose rates of 1 Gr / min. Injection of venom followed by gamma irradiation of 60Co at a dose of D = 1, 3, 5 and 7 Gy at an irradiation dose rate of 1 Gy / min increased the life span of the experimental groups of mice ranging from 45% to 56 % and from 52% to 67%, respectively. An increase in the lifespan of experimental rats exposed to radiation with the preliminary introduction of the venom of the honey bee.

Study of mechanisms on vason-strengthening action of flavonoids

Based on the analysis of the spectra, it has been found that compounds of flavonoid nature, binding to cell membranes, change not in all cases the fluidity of membrane lipids depending on the cell type. Obviously, vascular tissue cells are a kind of "target cells" for these substances, i.e. there is a selectivity of flavonoids to certain tissues of organs. A particularly noticeable increase in the lipid fluidity of membranes was observed due to the addition of flavonoid glycosides - hyperoside, stachanoaceside and liquiritin to segments of venous tissue, which correlated with the high affinity of these substances to liposomes. The addition to the vessels of the metabolite quercetin - chalcone also led to a sharp increase in the lipid fluidity of cells of arterial and venous tissue, what suggests the presence of biological activity in flavonoid metabolites. One of the mechanisms of increasing the resistance of arterial and venous vessels under the action of flavonoid substances is an increase in the lipid fluidity of cell membranes of these vessels, which reduces the fragility of blood vessels and increases their flexibility and elasticity. The apparent contradiction between the rapid metabolism of many flavonoids in animals and the prolonged pharmacological action can be explained by the capability of their metabolites, such as chalcone, to increase the lipid fluidity of vascular cell membranes, changing their resistance to external influences. Reducing the fragility of the pulmonary vessels and increasing their flexibility and elasticity can have a positive effect on a human body in the fight against coronavirus.

Identification of benzydamine and its metabolit in the presence of certain anti-inflammatory non-steroidal drugs

The aim of the work. Currently, a large number of cases of non-medical use of benzydamine hydrochloride have been described. The identification of benzydamine and its metabolite, benzydamine N-oxide, in the presence of some non-steroidal anti-inflammatory drugs, has been insufficiently studied. Therefore, the development of a method for its identification in biological material is an urgent task. Materials and methods. The subjects of the study were benzydamine hydrochloride and its metabolite, as well as some non-steroidal anti-inflammatory drugs, which are its analogues in terms of pharmacological action. The studies were carried out by methods of thin layer chromatography and high-performance liquid chromatography. Results. At the first stage a screening method for benzydamine identification was studied using the extraction in acidic and basic conditions. It was shown that benzydamine can be isolated in both medias with subsequent development with a solution of iodoplatinate and Dragendorff's reagent according to Munier or with Mandelin reagent respectively. The mobile phase was selected and respective hRf for the target molecule were defined. After a preliminary identification of benzydamine a reference method for the final confirmation of the drug that had led to poisoning was proposed. A robust, specific and accurate reversed phase HPLC method was chosen. It was shown that benzydamine exists in biological material mainly in a form of metabolite – benzydamine N-oxide. The selected method was able to separate and determine key analytes in biological samples after a preparative isolation by TLC method. The comparison with UV spectra of the reference standard of benzydamine hydrochloride was proposed to avoid false positive conclusion of drug identification. Conclusions. Proposed methodology can be applied for routine identification of benzydamine poisoning in toxicological laboratories

In silico drug repurposing of anticancer drug 5-FU and analogues against SARS-CoV-2 main protease

The pressing need to find effective drugs against the current deadly COVID-19 disease has recently motivated numerous studies using different approaches to address the problem. One time-saving and less costly strategy is the drug repurposing, which consists in finding new therapeutic uses for approved drugs. Following the same trend, this study has investigated the potential inhibitory activity of 5-FU and its analogues against the SARS-CoV-2 main protease as well as their profile of druggability using molecular docking and ADMET methods. From the calculations performed, four candidates showed promising results with respect to the binding affinity to the target protease, 3CLpro, the therapeutic profile of druggability and safety. Further in-vitro and in-vivo investigations are needed that may clarify their possible mechanism of the pharmacological action to combat COVID-19.

Development of Genistein Synthesis for Use as a Certified Reference Material

Introduction. The use of certified reference materials (CRMs) ensures metrological traceability and comparability of analysis results performed in different laboratories, by different analysts, at different times. Genistein is a promising substance with a wide spectrum of pharmacological action. genistein is widely used in dietary supplements. Development of regulatory documents for CRM of genistein will ensure the quality of drugs and dietary supplements.Aim. Aim of our study is to improve of the ways of synthesis and determination of spectrum characteristics of genistein for the certification of CRM.Materials and methods. We used synthetic genistein, (Ph.D. V. Yu. Kovtun SPC "Pharmzashchita") (sample № 1) and genistein synthesized and studied at the departments of pharmaceutical chemistry and chemical technology of medicinal substances SPCPU (sample № 2). Infrared spectra of genistein samples were collected on an FSM 1201 infrared Fourier spectrometer (OOO Infraspek, Russia) via KBr pellets technique. All the spectra were collected in the 4000–500 cm−1 range. The NMR (1H and 13C) measurements were performed with a BrukerAvance III NMR spectrometer (400 and 100 MHz) (Bruker, Germany) in DMSO-d6 solvent. Raman spectra were recorded by an ORTES-785TRS-2700 analytical Raman scattering system at a laser power of 100 mW (OPTEC JSC, Russia). Laser interaction time was 5, 10, 20 and 60 seconds. The results were processed using the software "BWSpec 4.10_4", USA. GC-MS was performed on an Agilent Technologies 7890A gas chromatograph (Agilent Technologies, USA) with a 7693 autoinjector and a Hewlett Packard 5975C mass selective detector.Results and discussion. The synthesis was carried out according to the developer's method. The stage "removal of the alkyl protection" has been improved. The spectra of the synthesis intermediate of genistein (biochanin A) correspond to the literature data. Samples of genistein were investigated by methods: MC and NMR 13С, 1Н. The structure of the investigated substance was confirmed; Raman and IR spectroscopy showed that the spectra of the samples do not differ from each other and there are no additional signals.Conclusion. The spectrum characteristics of samples of genistein were obtained by NMR, IR and Raman spectroscopy, which will be used in the regulatory documentation for CRM of genistein. All of this will make it possible to control the quality of medicines based on it and to identify substandard dietary supplements.