СИНТЕЗ ТА ОЦІНКА ПРОТИПУХЛОВОЇ АКТИВНОСТІ 2-АМІНОІЗОІНДОЛ ТІАЗОЛІДИНОНОВИХ ГІБРИДІВ

УДК 547.789.1:615.012.1]073/.076

Мета роботи. Синтез похідних 2-аміноізоіндол тіазолідинону шляхом реакції [2+3]-циклоконденсації шляхом використання різноманітних еквівалентів діелектрофільного синтону [C2]2+ та скринінг протипухлинної активності синтезованих сполук in vitro.Матеріали і методи. Органічний синтез, ЯМР спектроскопія, фармакологічний скринінг in vitro.Результати й обговорення. Шляхом реакції [2+3]-циклоконденсації 1-(1,3-діоксоізоіндолін-2-іл)тіосечовини з монохлороцтвою кислотою, N-арилмалеімідами і β-ароїлакриловими кислотами в середовищі льодяної оцтової кислоти було одержано 5-заміщені 2-аміноізоіндол тіазолідинонові гібриди. Синтез індолвмісних 2-аміноізоіндол тіазолідинонів було здійснено одностадійною трикомпонентною реакцією of 1-(1,3-діоксоізоіндолін-2-іл)тіосечовини, відповідного ізатину та монохлороцтової кислоти. Протиракова активність синтезованих сполук була вивчена в концентрації 10-5 M на панелі з 60 ракових клітин відповідно до стандартних протоколів Національного Інститут Раку (NCI, Bethesda, MD, USA) Developmental Therapeutic Program (DTP).Висновки. Досліджено ефективний метод синтезу нових ізоіндолтіазолідинонів. Індолвмісний 2-аміноізоіндолтизолідинон, продемонстрував помірний рівень протипухлинної активності з впливом на клітинні лінії меланоми, раку нирок і молочної залози.

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1,4-Naphthoquinone Motif in the Synthesis of New Thiopyrano[2,3-d]thiazoles as Potential Biologically Active Compounds

A series of 11-substituted 3,5,10,11-tetrahydro-2H-benzo[6,7]thiochromeno[2,3-d][1,3]thiazole-2,5,10-triones were obtained via hetero-Diels-Alder reaction of 5-alkyl/arylallylidene/-4-thioxo-2-thiazolidinones and 1,4-naphthoquinones. The structures of newly synthesized compounds were established by spectral data and a single-crystal X-ray diffraction analysis. According to U.S. NCI protocols, compounds 3.5 and 3.6 were screened for their anticancer activity; 11-Phenethyl-3,11-dihydro-2H-benzo[6,7]thiochromeno[2,3-d]thiazole-2,5,10-trione (3.6) showed pronounced cytotoxic effect on leukemia (Jurkat, THP-1), epidermoid (KB3-1, KBC-1), and colon (HCT116wt, HCT116 p53-/-) cell lines. The cytotoxic action of 3.6 on p53-deficient colon carcinoma cells was two times weaker than on HCT116wt, and it may be an interesting feature of the mechanism action.
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Detailing the Ten Main Professional Roles of a Pharmacist to Provide the Scope of Professional Functions

As members of a public trust profession, pharmacists are the most accessible medical team members. Therefore, every pharmacist must know the scope of their professional roles (PR) and professional functions (PF). The study aimed to detail the major PR into a pooled set of PF. The research materials were the provisions of the World Health Organization, the International Pharmaceutical Federation, and scientific works on the PR of pharmacists. Methods of critical analysis, concretization, functional decomposition, and scientific generalization were used. As a result of detailing the 10 main PR according to the “ten-star pharmacist” concept for each, a combined set of partial PFs of the pharmacist was obtained. The decomposition takes into account the principle of complexity limitation, which allowed three to six partial PF for the respective PR to be obtained, namely: three PFs for a life-long-learner, five PFs for a caregiver, a decision-maker, a teacher, a leader, a researcher, an entrepreneur, and an agent of positive change, six PFs for a communicator and a manager. Thus, due to the decomposition of each of the 10 main PR of the pharmacist into three or six corresponding partial PFs, we received a multifunctional verbal model of difficult to organize, professional activities, which is identified by a total of 50 PFs. The importance of using this model in formulating professional competencies and learning outcomes of educational programs for pharmacists is emphasized.
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3-[5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl]-propionic acid as potential polypharmacological agent

Abstract: Searching for new types of biological activities among preliminarily identified hit compounds is a key challenge in modern medicinal chemistry. In our study, a previously studied 3-[5-(1H-indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl]-propionic acid (Les-6614) was screened for antimicrobial, antifungal, anti-allergic and antitumor activities. Moreover, cytotoxicity, molecular docking, and, the SwissAdme online target screening were accomplished. It was determined that the Les-6614 has slight antimicrobial and antitumor activity. However, the studied compound decreased IgE levels in sensitized guinea pigs by 33-86% and reduced IgA, IgM, IL-2, and TNF-α, indicating anti-inflammatory and anti-allergic activities. According to the SwissADME web tool, target predictions Les-6614 potentially has an affinity for Lysosomal protective protein, Thromboxane-A synthase, and PPARγ. The molecular docking confirmed that the studied 2-thioxo-4-thiazolidinone derivative showed good bonding with LLP and TXAS leading to stable protein-ligand complexes. Also, the Les-6614 is a potential PPARγ modulator, which is important in the pathogenesis of allergy, cancer, and cardiovascular diseases.

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Microbial biofilms and some aspects of anti-inflammatory drug use

The review presents literature data on the effect of nonsteroidal anti-inflammatory drugs  (NSAIDs) on the formation of bacterial biofilms. The role of biofilm structures as a factor of  virulence of microorganisms is shown, and the protective reactions of a macroorganism in  infectious processes caused by bacteria — producers of biofilms are characterized. The article  also provides the examples of methods for studying biofilm formation and strategies for managing this process. The prospects of further study of the complex interaction between bacterial pathogens in biofilms are shown, which may help to develop further therapeutic strategies  against the biofilm-dependent infections.
K e y w o r d s: NSAIDs, microbiota, dysbiosis, prostanoids, cyclooxygenase, biofilms


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