In this work, the title compound was synthesized via the Claisen–Schmidt condensation of a 2-((5-acetyl-4-methylthiazol-2-yl)amino)isoindoline-1,3-dione with 2-fluorobenzaldehyde. The structure of the synthesized compound (yield 62%) was confirmed by 1H, 13C NMR, and LC–MS spectra. According to US NCI protocols, the compound displayed a high level of antimitotic activity against tested human tumor cells, with mean GI50/TGI values of 15.72/50.68 μM. The drug-like properties of the synthesized compound were evaluated using SwissAdme, revealing satisfactory drug-like parameters, and it presents interest for the design of new synthetic agents with biological activity.
A range of hybrid molecules incorporating the ciminalum moiety in the thiazolidinone ring demonstrate significant anticancer and antimicrobial properties. Therefore, the aim of our study was to evaluate the properties and mechanism of action of two 4-thiazolidinone-based derivatives, i.e., 3-{5-[(Z,2Z)-2-chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}propanoic acid (Les-45) and 5-[2-chloro-3-(4-nitrophenyl)-2-propenylidene]-2-(3-hydroxyphenylamino)thiazol-4(5H)-one (Les-247). In our study, we analyzed the impact of Les-45 and Les-247 on metabolic activity, caspase-3 activity, and the expression of genes and proteins related to inflammatory and antioxidant defenses and cytoskeleton rearrangement in healthy human fibroblasts (BJ) and a human lung carcinoma cell line (A549). The cells were exposed to increasing concentrations (1 nm to 100 μM) of the studied compounds for 24 h and 48 h. A decrease in the metabolic activity in the BJ and A549 cell lines was induced by both compounds at a concentration range from 10 to 100 μM. Both compounds decreased the mRNA expression of NRF2 (nuclear factor erythroid 2-related factor 2) and b-actin in the BJ cells. Interestingly, a significant decrease in the level of NF-kB gene and protein expression was detected in the BJ cell line, suggesting a direct impact of the studied compounds on the inhibition of inflammation. However, more studies are needed due to the ability of Les-45 and Les-247 to interfere with the tubulin/actin cytoskeleton, i.e., a critical system existing in eukaryotic cells.
UDC: 547.673.5+547.789.13
Synthesis and study of new polyfunctionalized 2-hydrazinoanthraquinone derivatives as potential antimicrobial agents. Methods. Organic synthesis, NMR and LC-MS spectroscopy, agar diffusion and broth microdilution methods. Results. A series of anthraquinonehydrazone derivatives are synthesized using the reaction of 2-(morpholinodiazenyl)anthracene-9,10-dione with methylene active compounds in the acetic acid medium. The screening of antimicrobial activity identified the compounds with significant effects against the tested microorganisms with MIC value <186.9 μM. Compounds 5 and 11 with MIC <93.5 μM are effective against yeast fungi whereas compound 5 with MIC <186.9 μM is effective against P.putida, which is multidrug resistant to antibiotics.
Development of cancer drug-resistance is still an ongoing problem in the modern anticancer treatment. Therefore, there is a need to search for a new active substance, which may become a potential anticancer agent. 4-Thiazolidinones are well-described substances with cytotoxicity against cancer cells in vitro. Therefore, the aim of this study was to evaluate the effect of two 4-thiazolidinone-based derivatives (Les-2769 and Les-3266) on the PPARγ-dependent cytotoxicity in normal human skin fibroblasts (BJ) and squamous cell carcinoma (SCC-15) in vitro. The data obtained showed a cytotoxic effect of Les-2769 and Les-3266 used in micromolar concentrations on SCC-15 and BJ cells, manifesting by a decrease in the metabolic activity, an increase in the release of lactate dehydrogenase, and caspase-3 activity. The co-treatment of the cells with Les-3266 and an antagonist (GW9662) or an agonist (rosiglitazone) of the PPARγ receptor induced changes in the above-mentioned parameters in the BJ and SCC-15 cells, compared to the Les-3266 alone exposure; this was not found in the Les-2769-treated cells. The further analysis of the compounds indicated changes in the expression of the PPARγ, KI67, and NF-κB genes. Moreover, the tested compounds caused an increase in the level of PPARγ mRNA expression in a similar way to rosiglitazone in SCC-15, which may indicate the affinity of the compounds for PPARγ. Molecular docking is consistent with experimental in vitro data about the potential agonistic activity of Les-2769 and Les-3266 towards PPARγ receptors. Summarizing, the anticancer effect of both compounds was observed in the SCC-15 cells in vitro; moreover, the mechanism of action of Les-3266 in cells is mediated probably by interaction with the PPARγ receptor pathway, which needs in-depth study.
Проведено аналіз впровадження прозорої системи оцінювання результатів діяльності науковців Львівщини за 2020-2021 роки. Запропонований підхід є зручним у формуванні бази даних, розрахунках та розумінні одержаних результатів і може бути з успіхом використаний для впровадження на регіональному чи загальнодержавному рівні. Аналіз результатів демонструє, що понад 60 % наукових праць, що забезпечують досягнення належного рівня наукометричних показників, досягаються завдяки статтям у сфері фізико-математичних. хімічних, біологічних та технічних досліджень. Зазначені дані є підставою для вдосконалення системи фінансування університетів та наукових закладів залежно від показників наукових досягнень, що сприятиме зростанню ефективності використання бюджетних коштів та підтримці перспективних напрямків досліджень. Показники, отримані у результаті впровадження відкритої системи оцінювання результатів діяльності науковців Львівщини, можуть бути використані як один з аргументів для розроблення пропозицій до плану оптимізації мережі закладів вищої освіти.