Пошук потенційних інгібіторів SARS-CoV-2 за допомогою in silico методів

Aim. Using in silico technologies to search for potential SARS-CoV-2 inhibitors among novel tetracyclic ring systems, which are the common core of Crinipellin.Materials and methods. The study object was new compounds previously synthesized via oxidative dearomatization of Crinipellin A. The method of the flexible molecular docking was applied in the study.Results and discussion. Using the molecular docking, the affinity of five compounds for the receptor-ACE2 SARS-CoV-2 (PDB ID: 7DF4), a spike protein SARS-CoV-2 (PDB ID: 1WNC), a PL protein SARS-CoV-2 (PDB ID: 7CJD) and a reverse transcriptase enzyme SARSCoV-2 (PDB ID: 6YYT) was studied. The results of the molecular docking obtained suggest that 8,8-dimethyl-5-(phenylsulfonyl)-3,3a,4,5,8,9-hexahydroindeno[3a,4-b]furan-2(7H)-one may be a potential SARS-CoV-2 inhibitor; it is the basis for its further experimental pharmacological study.Conclusions. The study constitutes one of the stages of searching for SARS-CoV-2 inhibitors. According to the results obtained, a way to search for potential SARS-COV-2 inhibitors based on Crinipellin A derivatives was proposed. Using the most promising compound with hexahydroindeno[3a,4-b]furan core further studies open up another direction for searching for compounds of SARS-COV-2 inhibitors and will save time and laboratory animals while conducting targeted experimental research.Мета роботи. За використання in silico технологій здійснити пошук потенційних інгібіторів SARS-CoV-2 серед нових тетрациклічних кільцевих систем, які є загальним ядром криніпеліну.Матеріали та методи. Об’єктом дослідження є п’ять нових сполук, одержаних шляхом деароматизації криніпеліну А і синтезованих у попередніх дослідженнях. В in silico дослідженнях використано метод гнучкого молекулярного докінгу.Результати та їх обговорення. Шляхом використання докінгових досліджень вивчено афінітет п’яти сполук до рецептора-ACE2 SARS-CoV-2 (PDB ID:7DF4), spike протеїну SARS-CoV-2 (PDB ID: 1WNC), PL протеїну SARS-CoV-2 (PDB ID: 7CJD) та ферменту зворотної транскриптази SARS-CoV-2 (PDB ID: 6YYT). Одержані результати докінгових досліджень дозволяють стверджувати, що 8,8-диметил-5-(фенілсульфоніл)-3,3a,4,5,8,9-гексагідроіндено[3a,4-b]фуран-2(7H)-он може бути потенційним інгібітором SARS-COV-2, що є підставою для його подальшого експериментального фармакологічного вивчення.Висновки. Подане дослідження є одним з етапів пошуку інгібіторів SARS-CoV-2. З огляду на одержані результати запропоновано шлях пошуку потенційних інгібіторів SARS-COV-2 на основі похідних крініпеліну А. Подальші дослідження з використанням найбільш перспективної похідної гексагідроіндено[3a,4-b]фурану відкривають ще один напрям пошуку сполук інгібіторів SARS-COV-2 та дають можливість заощадити час і лабораторних тварин у межах виконання цілеспрямованих експериментальних досліджень у майбутньому

Control of the Nanoparticles Content in Cosmetic Medicines

The safety of nanoparticles used in medical cosmetology and dermatology raises significant concerns. One of the tasks of analyzing the concentration of nanoparticles that must be solved for the practical analysis of the quality of products with nanoparticles is the quantitative analysis of the content of nanoparticles. The previously developed acousto-magnetic method (AMM) for determining the concentration of APIs as magnetic nanoparticles can be used to determine the nanoparticles' concentration when samples are prepared as a colloidal solution. It is shown that the described method not only can be applied for quality control in cosmetology and dermatology but also can be simplified by using a less sensitive magnetometer, which makes this direct method more available in the entire range of values ​​of the concentration of magnetic nanoparticles used in medical cosmetology and dermatology

Features of Standardization and Registration of Dietary Supplements Compared to Drugs

The constant increase in the number of dietary supplements and the demand for them, as well as the progression of self-medication with the use of over-the-counter medicines, raises questions about their effectiveness, safety and bioequivalence. There are also questions about the criteria for ingredients, production, standardization and registration of finished medicines and dietary supplements.The aim. The aim of the work is to summarize information on the features of standardization, certification and registration of dietary supplements in comparison with drugs in the territory of Ukraine.Materials and methods. Data were collected and analyzed from the current scientific literature and regulatory documents to perform the research.Results. Production, standardization and circulation of finished medicines and dietary supplements is carried out in accordance with the current legislation of Ukraine, International standards (ISO, ICH, GxP) and the requirements of the State Pharmacopoeia of Ukraine. According to these documents, the requirements for the quality of medicines and dietary supplements differ, but unlike ten years ago, today there can be increased regulation and control on the part of the state and law enforcement agencies to eliminate cases of falsification and circulation of unregistered means.The current legislation of Ukraine regulating the production, quality and circulation of finished medicines harmonized with the EU puts forward requirements for providing the population with quality imported / domestic medicines. Regarding dietary supplements, the procedure of harmonization of the legislation of Ukraine with the EU has started, which in the future should lead to improvement of the quality of these remedies and increase of control from the state.Discussion. We generalized requirements for the features of standardization and registration of dietary supplements in the territory of Ukraine, which must be observed in the manufacture, quality control, registration and sale of dietary supplements.Conclusions. Simpler registration, implementation and wider market conditions (multi-level marketing system, Internet) lead to a rapid increase in the production of dietary supplements in Ukraine and their imports. We generalized information about the requirements for the quality of dietary supplements in comparison with finished medicines, and the features of their registration in the territory of Ukraine according to the current legislatio

Development of Determination Methods of Quetiapine Fumarate for Forensic-pharmaceutical Purposes

Quetiapine fumarate (an antipsychotic) is part of numerous generic drugs that are in fairly wide demand among the population, therefore, more and more data appear on the counterfeiting and smuggling of funds, as well as non-medical use, which are life-threatening for the population and explain the high prevalence of the active ingredient as object of forensic examination. The aim. To develop an algorithm for conducting a forensic pharmaceutical examination and propose a method for determining quetiapine fumarate for forensic pharmaceutical purposes. Materials and methods. All studies were performed using reagents that meet the EP, USP and USPU requirements, Class A glassware and qualified devices. Identification by IR spectroscopy was performed in the range from 500 to 4000 cm-1 on the device “Nicolet 380 FT-IR Spectrometer by Thermo Fisher Scientific” using a prefix “Smart Perfomer” with a ZnSe crystal. The UV absorption spectra of the solutions were recorded using a Specord 205 spectrophotometer from Analytik Jena AG (Germany). TLC was performed on Merck chromatographic plates (silica gel 60G F254, Germany). The following systems were used as mobile phases: hexane – acetone – 25 % ammonia solution (60: 40: 2); methanol – 25 % ammonia solution (100: 1.5), hexane – acetone – 25 % ammonia solution (50: 45: 5). Detection was performed under UV light (254 nm), followed by spraying with Dragendorff reagent. Analysis by gas chromatography with mass detection was performed using a GC gas chromatograph with a mass spectrometric detector GCMS-QP2020. Data were analyzed using the program: GCMSsolution, LabSolutions Insight (Shimadzu Corporation, Tokyo, Japan). Results. An algorithm for conducting a forensic pharmaceutical examination in accordance with the current legislation of Ukraine has been developed, methods for determining quetiapine for forensic pharmaceutical purposes have been proposed. Conclusions. The developed methods for determining quetiapine meet the requirements of the current legislation of Ukraine and the Ministry of Justice of Ukraine. The obtained data prove the high sensitivity and reproducibility of the methods and prove the possibility of their introduction into the practice of forensic examinatio

Structural Modification of Ciprofloxacin and Norfloxacin for Searching New Antibiotics to Combat Drug-resistant Bacteria

The aim of the work. Among all the representatives of four generations of fluoroquinolones ciprofloxacin (CIPRO) and norfloxacin (NOR) remain widely used and prescribed antibiotics in clinical practice. However, the problem of resistance towards them is gradually increasing. Thus, our investigation is dedicated to chemical modification of C-7 position of Ciprofloxacin and Norfloxacin ring as a promising solution to combat antibiotic resistance and open a pathway towards convenient synthesis of new fluoroquinolones derivatives. Materials and methods. The subjects of the research were N-piperazine-substituted ciprofloxacin and norfloxacin. The methods of molecular docking and organic synthesis were applied in the study. The structures of the obtained compounds were confirmed by 1H NMR, 13C NMR, 19F NMR, LC/MS, IR, UV spectroscopy. The antimicrobial activity was measured by the method of double serial dilutions against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Bacillus subtilis (ATCC 6633), Pseudomonas aeruginosa (ATCC 27853), Candida albicans (NCTC 885-653) and diffusion in agar method against clinical strains. The results. 7-(4-(2-Cyanoacetyl)piperazin-1-yl)-1-R-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acids were synthesized and their structures were confirmed. The obtained compounds showed the antibacterial activity on the reference level for double dilution method and exceeded control for “well” method. Conclusions. The current investigation revealed the promising route for the expanding of the existing fluoroquinolones diversity. Pharmacodynamics and pharmacokinetics changes could be achieved by chemical modifications of C-7 position of the initial ring. Further research utilizing the obtained compounds as starting ones opens a promising way to novel active molecules synthesis and combating the problem of antibiotic resistanc