A number of new biologically active phosphorus-containing quinones were prepared by the reaction of 2,3-dichloro-1,4-naphthoquinone and sodium 1,2-naphthoquinone-4-sulfonate with phosphonate nucleophilic reagents, aminophosphonic acid esters. The structures of the synthesized compoumds were confirmed by ESI-MS, 1H NMR, IR-spectroscopies and elemental analysis. It was shown that aminophosphonic esters form products of nucleophilic substitution of a chlorine atom of 1,4-naphthoquinone or a sulfonyl group of 1,2-naphthoquinone on an aminophosphonic fragment. The products of the interaction of sodium 1,2-naphthoquinone-4-sulfonate with primary aminophosphonates existed in solution in 1,2-quinoid or 2-hydroxy-1,4-quinonimine tautomeric form depending on pH. The antimicrobial activity of the prepared compounds was investigated against Escherichia coli В-906, Staphylococcus aureus 209-Р, Mycobacterium luteum В-917, Candida tenuis VKM Y-70 and Aspergillus niger VKM F-1119 strains by the method of diffusion in agar of their 0.1% and 0.5% solutions. 1,2-Naphthoquinone derivatives showed good activity against S. aureus at a concentration of 0.1%, in its turn 1,4-napthoquinone derivatives showed activity against M. luteum at a concentration of 0.5%.

A series of disperse dyes, 9,10-anthraquinone containing dithiocarbamate, thiourea and triazole fragments, were prepared via consecutive refunctionalization of aminoanthraquinones in our previous studies and their structures were confirmed by the 1H-, 13C-NMR, IR spectra, LC-MS and elemental analysis data. The obtained compounds were applied on polyester fabrics by the exhaustion method at 130°C at pH 4.0-5.0, and their dyeing properties were evaluated by color measurements, the washing fastness test and the light fastness test. Many of these dyes gave solid and level dyeings on polyester fabric with low % concentration of dye. The dyed samples displayed very good color fastnesses. The color change and staining test results were quite good with ratings of “4-5” or above. The light fastness test results were also satisfactory for the most of the dyed samples.

The regioselectivity of the reaction of 2-chloro- and 2,3-dichloro-5-substituted naphthoquinones with CH-acids is studied. It is shown that the nature of the substituent in 5-RO-1,4-naphthoquinones plays the main role in the predominant formation of one of the possible regioisomers in the reactions of nucleophilic substitution. It is substantiated that the orientation of the nucleophilic attack by CH-acid on the C3 atom of 5-RO-1,4-naphthoquinones is due to the fact that the 5-methoxy and 5-acetoxy groups have a passivating effect on the electron-accepting properties of the C4=O group due to the positive conjugation effect. As a result, the electrophilic center appears in position 3. It is established that the interaction of 2- or 3-chloro-substituted 5-RO-1,4-naphthoquinones with CH-acids proceeds with the formation of 2- and 3-addition products with a preference for products of substitution of the chlorine atom in 3rd position. The structure of the regioisomers is confirmed by spectral data and by countersynthesis.

The global emergence and dissemination of multidrug-resistant fungal and bacterial pathogens is a serious public health threat. The development of novel highly active antimicrobial compounds simultaneously targeting several targets in bacterial or fungal pathogens could help to fight antimicrobial resistance. The four-component one-pot two-step facile synthesis of a new 2-dithiocarbamate-N-(9,10-dioxo-9,10-dihydroanthracenyl)acetamides 3a-n by the interaction of 2-chloro-N-(9,10-dioxo-9,10-dihydroanthracenyl)acetamide 1 or 2 with a series of in situ generated potassium salt of dithiocarbamic acids in DMF-H2O is presented. Evaluation of the antimicrobial activity of the synthesized compounds against bacteria strains Escherichia coli В-906, Staphylococcus aureus 209-Р, Mycobacterium luteumВ-917, and fungi Candida tenuis VKM Y-70, Aspergillus niger VKM F-1119 has been carried out by the diffusion in agar method and by the serial dilution technique. It has been established that synthesized compounds 3a, 3i, 3j have the good antibacterial activity against strain M. luteum at a concentration of 0.5% and the dithiocarbamates 3b, 3i, 3j, 3n demonstrate antifungal effect against C. tenuis at the same concentration. The results of the serial dilution technique showed that compound 3j has high antibacterial action at MIC 3.9 μg/ml.

The article presents the results of the analysis of alternative methods of studying theGood Pharmaceutical Practice complex, introduced at the Lviv Polytechnic National University.The optimal structure of the curriculum for student’s education by the specialty 226 “Pharmacy,Industrial Pharmacy” was determined to improve the system of training of specialists,who need understand the current pharmaceutical legislation of Ukraine and prospects for itsdevelopment.Structural-and-logical schemas based on the Guidelines of Good Pharmaceutical Practicesthat greatly facilitate students’ perception and assimilation of all the needed informationhave been elaborated.The development of such schemes by students with teacher assistance allows to improvethe perception of the material and strengthen skills for independently analyzing. While performingthe task, students to learn and understand certain aspects, such as the fact that the quality ofthe medicines is “incorporated” into the drug at the stage of pharmaceutical development, andthen confirmed during preclinical and clinical research. Further, the medicine receives a “permitto life”, when passing state registration. After that, the specified quality is reproduced for eachseries at the stage of full-scale pharmaceutical manufacturing, it is maintained unchanged at thestages of storage and distribution and, finally, it is delivered to patients in pharmacies. The study of the possibility of mastering the discipline “Good Practices in Pharmaceutics”by students of specialty 226 “Pharmacy, Industrial Pharmacy” during the practice at theexisting pharmaceutical enterprises can be considered perspective.

Biochemical and microbiological changes in processes of fermentation and storage of fermented milk product prepared using Tibetan kefir grains were studied. Principal stages for the production of feed additive were depicted in biotechnological and technological schemes with equipment. Technological parameters, conditions of cultivation and fermentation were selected to manufacture product in industrial scale.

Onychomycosis is one of the most acute problems of modern medicine, which accounts for about 50% of all nail diseases. Fungi of dermatophytes of the genus Trichophyton are the most studied etiological factor of onychomycosis. Non-dermatophytes can also cause onychomycosis. Fungi of the genus Aspergillus is one of the main pathogens among the non-dermatophytes agents of onychomycosis. Antifungal nail lacquer is the most optimal dosage form for the topical treatment of onychomycosis. GABA derivative of 2-chloro-N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)acetamide was used as a perspective antifungal agent in the form of lacquer. The antifungal action of the obtained lacquer containing compound 2 against fungus strain Aspergillus niger VKM F-1119 was compared with the known antifungal lacquer Lamisil containing terbinafine as the active agent. Investigation of the antifungal action was carried out at concentrations of 1%, 0.5%, and 0.1% of compound 2 and terbinafine using the diffusion in agar technic after 24 h and 72 h. It has been determined that derivative 2, as well as terbinafine at a concentration of 1%, caused fungicidal action after 24 h and fungicidal and fungistatic effect after 72 h.

Neuroinflammation is an integral part of epilepsy pathogenesis and other convulsive conditions, and non-steroidal anti-inflammatory drugs (NSAIDs) present a potent tool for the contemporary search and design of novel anticonvulsants. In the present paper, evaluation of the anticonvulsant activity of the potential NSAID dual COX-2/5-LOX inhibitor darbufelone methanesulfonate using an scPTZ model in mice in dose 100 mg/kg is reported. Darbufelone possesses anticonvulsant properties in the scPTZ model and presents interest for in-depth studies as a possible anticonvulsant multi-target agent with anti-inflammatory activity. The series of 4-thiazolidinone derivatives have been synthesized following the analogue-based drug design and hybrid-pharmacophore approach using a darbufelone matrix. The synthesized derivatives showed a significant protection level for animals in the scPTZ model and are promising compounds for the design of potential anticonvulsants with satisfactory drug-like parameters.

As a result of the carried out research it was synthesized an order of new potentially biologically active modified N-,O-contained heterocycles on the base of amino acid derivatives of 2,6,7-nitrogen substituted-3-chloro-1,4-naphthoquinone. It was established that among synthesized compounds, there are potential antimicrobial substances with high activity.

International scientific and practical conference «New trends and unresolved issues of preventive and clinical medicine» : Conference proceedings, September 25–26, 2020. Lublin : Izdevnieciba «Baltija Publishing», 2020. 428 pages.

Novel 2,3,4,9-tetrahydro- and 4,9-dihydro-1H-benzo[f]isoindole derivatives were synthesized from Juglone and amino-acid azomethines in 74-85% yields via 1,3-dipolar cycloaddition. The stereo- and regioselectivity of cycloaddition was confirmed by NMR spectra and single-crystal X-ray diffraction analysis.

The analysis of the range of drugs containing raw materials and biologically active compounds Pinus sp. registered in Ukraine and found: most drugs are presented in the form of ointments; the predominant share of the range (79%) of the studied drugs are multicomponent drugs; the share of the range of drugs manufactured at pharmaceutical enterprises of Ukraine is 38%; the largest number of drugs is manufactured by domestic manufacturers in the city of Zhytomyr PJSC "Liktravy" and LLC "DKP" Pharmaceutical Company; among importing countries, Germany dominates, followed by India and Estonia, respectively.

The nitro group-substituted perhalogenobuta-1,3-diene (1) is important synthetic precursor in the synthesis of different heterocycles groups with high biological activity. Firstly, new N,S-substituted-perhalonitro-1,3-butadiene compounds were synthesized by the reactions of various amino or thiol containing nucleophiles with1. The structures of all new compounds have been identified by using spectroscopic techniques (FT-IR,H-1-NMR,C-13-NMR, MS and microanalysis). Secondly, their antimicrobial properties were tested as potential antibacterial and antifungal agents. Antimicrobial activity of synthesized N,S-substituted perhalonitrobutadienes4a-jand5a-dwas evaluated againstEscherichia coliB-906,Staphylococcus aureus209-P, andMycobacterium luteumB-917 bacteria andCandida tenuisVKM Y-70 andAspergillus nigerF-1119 fungi and the compounds4c,4d,5aand5bwith high antifungal action against test-cultureAspergillus nigerat MIC values 0.9-1.9 mu g/cm(3)were identified as the most potent.

Мета роботи. Ввести в культуру in vitro Delphinium elatum L., дослідити вплив регуляторів росту на процеси росту рослинних клітин, визначити оптимальні умови культивування рослини в умовах in vitro. Одержати екстракти біомаси та рослинної сировини D. elatum, провести порівняльне дослідження вмісту біологічно активних сполук, антимікробної та антиоксидантної активностей. Матеріали і методи. Культивування D. elatum проводили на модифікованому живильному середовищі Мурасіге-Скуга. Екстракти одержували методом мацерації, як екстрагент використовували водно-етанольні розчини в концентрації 20, 40, 70 та 90 %. Загальний вміст фенольних сполук в екстрактах визначали спектрофотометричним методом Фоліна-Чокальтеу, загальний вміст флавоноїдів – колориметричним методом з алюмінію хлоридом. Антимікробну активність досліджували на стандартних та клінічних штамах мікроорганізмів методом дифузії в агар, антиоксидантну активність – спектрофотометричним методом шляхом взаємодії зі стабільним хромоген-радикалом 2,2-дифеніл-1-пікрилгідразилом. Результати й обговорення. Підібрано оптимальну схему стратифікації та стерилізації насіння D. elatum з найбільшим виходом асептичних експлантів: почергові механічна обробка, змочування холодною стерильною водою, витримка в холодильнику, обробка 70 % етанолом, натрію гіпохлоритом та стерилізованою бідистильованою водою. Визначено склад поживного середовища Мурасіге-Скуга, доповненого регуляторами росту БАП, 2,4-Д, на якому спостерігались найвищі значення індексу росту і найменший час подвоєння біомаси калюсів. Одержано калюсну біомасу після 35 діб культивування. Досліджено загальний вміст флавоноїдів та фенольних сполук в екстрактах D. Elatum. Встановлено, що екстракти як калюсної біомаси, так і рослинної сировини, одержані з 40 % водно-етанольним розчином мають найбільший вміст фенольних сполук і флавоноїдів. Встановлено протимікробну та протигрибкову активність екстрактів D. elatum щодо стандартних та клінічних штамів деяких мікроорганізмів. Визначено, що максимальну активність проявили екстракти D. elatum, одержані з 40 % та 70 % водно-етанольними розчинами. Висновки. У результаті проведених досліджень встановлено, що калюсна біомаса D. elatum за вмістом фенольних сполук, флавоноїдів та фармакологічною активністю не поступається рослинній сировині і може бути використана як рівноцінна лікарська сировина.

Background : Anthraquinone derivatives, frequently occurring motifs in many various natural compounds, have attracted a great deal of interest as compounds with a wide spectrum of biological activities. Introduction: The hybrid pharmacophore approach has become an object of considerable interest due to the incorporation of a five- or six-membered heterocyclic rings in the structure of various natural compounds, especially anthraquinone derivatives. Methods: A series of polyfunctionalized anthraquinonehydrazones have been synthesized via the azo-coupling reaction between anthraquinone-based triazenes and methylene active compounds. The structures of synthesized compounds were confirmed by spectral data. Some of the synthesized compounds were screened for their in vitro anticancer activity according to US NCI protocols. The screening of antimicrobial and antifungal activities against Candida albicans and Lactobacillus sp. was carried out. The synthesized compounds were evaluated for their antioxidant (DPPH free radical scavenging assay) and herbicidal activity. Results: The synthesized 1-[N'-(5-oxo-2-thioxoimidazolidin-4-ylidene)-hydrazino]-anthraquinone 1.5 displayed a high level of antimitotic activity against tested human tumor cells with mean GI50/TGI values 4.06/78.52μM. The screening of antimicrobial and antifungal activities led to the identification of 1.8 and 1.9 with a moderate effect on Candida albicans and Lactobacillus sp. Antioxidant activity evaluation allowed the identification of 1-[N'-(3-methyl-5-oxo-1-phenyl-1,5- dihydropyrazol-4-ylidene)-hydrazino]-anthraquinone 1.8 with an IC50 value of 3.715 mM. The herbicidal activity screening led to compound identification 1.8 with growth inhibition of Agrostis stolonifera at 25 %. Conclusion: The obtained anthraquinonehydrazones constitute an interesting template for the design of new synthetic agents with polypharmacological activities.

Мета роботи. Провести анатомо-морфологічне дослідження надземної частини пахучки звичайної (Сlinopodium vulgare L.) з родини Глухокропивові ( Lamiaceae Martinov) та встановити її діагностичні ознаки. Матеріали і методи. Препарати для мікроскопічного дослідження виготовляли з фрагментів трави пахучки звичайної, заготовленої у період цвітіння, і обробляли у суміші етиловий спирт: гліцерин: вода у співвідношенні 1:1:1 впродовж трьох діб. Окрім того, у ході експерименту використовували тимчасові препарати трави рослини, які фіксували у розчині хлоралгідрату. При проведенні макроскопічного аналізу користувались діючою нормативною документацією «Трави» ДФУ. Підготовлені для аналізу фрагменти трави поміщали на скляну пластину або предметні скельця, ретельно їх розправляли і розглядали спочатку неозброєним оком, а потім з допомогою лупи (10х) та мікроскопа «Біомед 6» (10х, 40х, 100х). Використовували не менше ніж 15 зразків кожної серії трави рослини, заготовлених у двох областях України - Львівській та Івано-Франківській. Результати й обговорення. На основі проведеного морфолого-анатомічного дослідження фрагментів листків, стебел та квіток Сlinopodium vulgare встановлено наявність специфічних трихом епідерми, особливості локалізації ефірних олій та характерні ознаки поперечних зрізів стебел і листків та забарвлення віночка квіток. Діагностичними мікроскопічними ознаками трави рослини можна вважати трихоми епідерми, які представлені простими дво- і триклітинними волосками, а також залозистими волосками, що мають двоклітинну головку; присутні також ефіроолійні залозки. Характерною ознакою є те, що по краю листкової пластинки зустрічаються прості одно- та двоклітинні волоски. Листок рослини амфістоматичного типу; клітини нижньої епідерми мають дещо менші розміри, ніж верхньої; продихи у верхній епідермі зустрічаються поодиноко, у той час як у нижній – у значній кількості. Ефіроолійні залозки зосереджені переважно у нижній епідермі листка. Стебло рослини пряме, короткоопушене, чотиригранне. Листки дрібні, яйцеподібні або видовжено яйцеподібні, довжиною 2-5 см, по краю дрібнорубчасто-пильчасті, волохато-волосисті від опушення, знизу – світло-зелені; листорозміщення супротивне. Листки, стебла і генеративні органи густо вкриті волосками і характерними ефіроолійними залозками. Квітки неправильні, дрібні, щетиновидно-лінійні, з густовійчастими приквітками, в 15-40-квіткових кільцях, що утворюють півкулясті суцвіття. Чашечка трубчаста, з багатьма жилками, густо опушена, з шиловидними зубцями. Віночок двогубий, різних відтінків фіолетово-пурпурового кольору, до 15 мм завдовжки, удвічі довший, ніж чашечка. Забарвлення віночка квіток при зростанні рослини у Львівській обл. варіює від світло-пурпурового до фіолетово-пурпурового, у Івано-Франківській обл. він завжди фіолетово-пурпуровий. Верхня губа віночка коротка, дволопатева, нижня – трилопатева. Андроцей двосильний, складається з чотирьох тичинок, що приростають до трубки віночка. Біля основи зав’язі є нектароносний диск. При проведенні якісної реакції на вміст ефірних олій з використанням Судану III їх максимальну локалізацію зафіксовано у ефіроолійних залозках нижньої епідерми листка. Висновки. Таким чином, встановлено характерні морфологічні та анатомічні діагностичні ознаки листків, стебел та квіток пахучки звичайної з родини Глухокропивові як лікарської рослини народної медицини, яка поширена в Львівській та Івано-Франківській областях України в дикорослому стані та є перспективною для подальшого вивчення та використання у фармації.

This work describes the synthesis and a convenient method for obtaining new 1,2,4-triazine-and 1,2,4-triazole-containing 1,4-naphthoquinone derivatives.The studied 1,5-binucleophiles react with 1,4-naphthoquinone via only one nucleophilic center of the molecule, the aniline fragment.2-(2-(6-aryl-5-oxo-2,5dihydro-1,2,4-triazin-3-yl)phenyl) amino) naphthalene-1,4-dione and 2-((2-(3-aryl-1H-1,2,4-triazol-5-yl)phenyl) amino) naphthalene-1,4-diones were prepared by bonding of an amino group to the electron -deficien t double bond of 1,4-naphthoquinone followed by oxidation of formed 1,4-diol with an excess of 1,4-naphthoquinone.The biological activity of the synthesized 1,2,4-triazine-and 1,2,4-triazole-containing 1,4-naphthoquinone derivatives was evaluated by using PASS Online and Gusar software.High anticancer and antimicrobial activity and low toxicity of the obtained substances were predicted, which allows considering this class of organic compounds as a promising one in terms of preparation of new drugs.1,2,4-Triazole-containing naphthoquinone derivatives are likely to be histidine kinase inhibitors and may be promising antimicrobials.The conducted primary screening of biological activity and toxicity of the synthesized compounds testified to high expediency of further experimental studies of anticancer and antimicrobial activity in order to find new effective drug substances.

The characteristics of Viper's bugloss (Echium vulgare) plant, its pharmacological properties, and extracts’ composition are presented in this study. Results of the literature analysis, data on the biologically active compounds and areas of use of this medicinal plant are summarized. Viper's bugloss (E. vulgare) is a species of flowering plant in the borage family Boraginaceae. It is native to most of Europe as well as western and central Asia. Viper's bugloss (E. vulgare) is a plant that has been utilized as food (honey), medicine, a poison, an oil, and as a dye and tannin-producing ornamental plant. Viper's bugloss (E. vulgare) is especially rich in pyrrolizidine alkaloids, flavonoids, phenolcarboxylic acids, sterones and naphthoquinones. In traditional medicine, Viper's bugloss (E. vulgare) is utilized as exhilarant and a mood stimulant. That is why one of the possible uses of this plant is considered to be treatment of depressive states. Like most representatives of Boraginaceae family, it has been insufficiently studied. No previous work quantifying flavonoids content of aerial parts of Viper's bugloss (E. vulgare) growing in Ukraine has been presented. Continuing the studies of this species, the aqueous and ethanolic extracts from Viper's bugloss (E. vulgare) aerial parts were obtained and their phytochemical composition was investigated. For the first time, the qualitative analysis of biologically active compounds in Viper’s bugloss’s extract as well as the quantitative analysis of flavonoids by aluminum chloride spectrophotometric method are reported. The experimental results showed that the total concentration of flavonoids was 2.59% in the extract. The maximum yield of extractives was found to be 16%. The obtained research data will be used in future investigations.

Novel heterocyclic dichloronaphthoquinone derivatives have been synthesized by chlorine atom substitution in 2,3-dichloro-1,4-naphthoquinone to pyrazole or pyrimidine fragments. The structures of these compounds have been confirmed by FT-IR, ESI-MS, 1H‐NMR, 13C-NMR and elementary analysis. Synthesized compounds were evaluated for their anticonvulsant action in a pentylenetetrazole (PTZ)-convulsion model and antidepressant activity in the forced swimming test (FST). All naphthoquinone derivatives at a dose 100 mg/kg indicated anticonvulsant effect in PTZ-induced test at 3 h and 24 h after oral administration. In addition, these compounds possessed prolonged antidepressant properties significantly reducing the duration of immobility time when compared to the reference drug amitriptyline.

The aim. Analysis and synthesis of data on the area of growth, content of biologically active compounds and the spectrum of use in pharmacy and medicine Caltha palustris. Materials and methods. Literary and electronic sources of information regarding the distribution, chemical composition and pharmacological activity of Caltha palustris. Results. Caltha palustris is a perennial herb of the Ranunculaceae family. The plant is unofficial, widely used by folk medicine as an anti-inflammatory, antispasmodic, bactericidal, antimicrobial, analgesic, diuretic agent. The main biologically active substances of Caltha palustris are tannins, glycosides (γ-lactones of protoanemonin and anemonin), saponins, berberine, bitterness, vitamin C, choline, carotene, flavonoids and alkaloids. Caltha palustris is a regionally rare plant in the administrative territories of Ukraine. Given the relevance of expanding the range of medicinal plant raw materials for the creation of modern therapeutics and chemical composition, pharmacological action of Caltha palustris, it is advisable to conduct further resource, phytochemical and other studies of the plant. Conclusions. Considering the extensive experience in folk medicine, the wide range of pharmacological activity, the content of valuable biologically active compounds Caltha palustris is a promising and valuable raw material for the preparation and production of phytochemicals and their practical application