UDC: 615.277.3:547.78].012:542.9
In vitro study and characterization of anticancer activity of heterocyclic derivative — [3-allyl-4-(41-methoxyphenyl)-3H-thiazole-2-ylidene]-(32-trifluoromethylphenyl)amine hydrobromide
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.
New 4-aryl-3-(morpholin-4-yl)-2-arylimino-2,3-dihydrothiazole derivatives 1.1-1.16 were obtained using the Hantzsch reaction by condensation of N-(morpholin-4-yl)-N'-arylthioureas with the corresponding α bromoacetophenones in alcohols. Synthesized hydrobromides 1.1-1.8 were formed as crystalline precipitates during the boiling of the reaction mixture. Bases 1.9-1.16 were obtained by neutralizing the corresponding hydrobromides with NH4OH solution. It has been proposed a possible mechanism of the reaction that is based on the study of the structure of the synthesized compounds. The structures of the synthesized compounds were confirmed by 1H NMR spectroscopy with its special techniques (NOESY and ROESY experiments). It has been shown the formation of the isomer 4-(4'-chlorophenyl)-3-(morpholin-4-yl)-2-(4'-chlorophenylamino)-2.3-dihydrothiazole on the basis of compound 1.14. Pharmacological screening of synthesized derivatives of 4-aryl-2-arylimino-2,3-dihydrothiazole compounds revealed the analgesic effect in the model of visceral pain caused by the introduction of acetic acid to white mice. The anti-inflammatory effect of the synthesized compounds was evaluated in vivo by reducing limb edema in rats with carrageenan-induced inflammation. Thus, the synthesized compounds have analgesic and anti-inflammatory activity.
UDC 577.24:612.68:615.03:615.1
Розробка умов ідентифікації та кількісного визначення йохімбіну методом УФ-спектрофотометрії Осипчук Л.І.
Вивчено характер УФ-спектру та розрахувано показники поглинання йохімбіну в метанольних розчинах.