Heterocycles are commonly known for their unique features, e.g., antibacterial or anticancer properties. Although many synthetic heterocycles, such as 4-thiazolidinone (4-TZD), have been synthesized, their potential applications have not yet been fully investigated. However, many researchers have reported relevant results that can be a basis for the search for new potential drugs. Therefore, the aim of this study was to evaluate the cytotoxic, cytostatic, and antibacterial effects of certain 4-thiazolidinone-based derivatives, Les-3166, Les-5935, Les-6009, and Les-6166, on human fibroblasts (BJ), neuroblastoma (SH-SY5Y), epithelial lung carcinoma (A549), and colorectal adenocarcinoma (CACO-2) cell lines in vitro. All tested compounds applied in a concentration range from 10 to 100 µM were able to decrease metabolic activity in the BJ, A549, and SH-SY5Y cell lines. However, the action of Les-3166 was mainly based on the ROS-independent pathway, similarly to Les-6009. In turn, Les-5935 and Les-6166 were able to promote ROS production in BJ, A549, and SH-SY5Y cells, compared to the control. Les-3166, Les-6009, and Les-6166 significantly increased the caspase-3 activity, especially at the concentrations of 50 µM and 100 µM. However, Les-5935 did not induce apoptosis. Only Les-5935 showed a minor cytostatic effect on SH-SY5Y cells. Additionally, the antibacterial properties of the tested compounds against P. aeruginosa bacterial biofilm can be ranked as follows: Les-3166 > Les-5935 > Les-6009. Les-6166 did not show any anti-biofilm activity. In summary, the study showed that Les-5935, Les-6009, and Les-6166 were characterized by anticancer properties, especially in the human lung cancer cell. In cases of BJ, SH-SY5Y, and CACO-2 cells the anticancer usage of such compounds is limited due to effect visible only at 50 and 100 µM.

Новину відредагував: library-lnmu - 2-01-2025, 10:25

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.