PDF(Pubmed)
Abstract：
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 β-actin in the BJ cells. Interestingly, a significant decrease in the level of NF-κB 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.
摘要：
在噻唑烷酮环中掺入了西姆明矾部分的一系列杂化分子显示出显著的抗癌和抗微生物性质。因此,我们研究的目的是评估两种4-噻唑烷酮类衍生物的性质和作用机理，即，3-{5-[(Z,2Z)-2-氯-3-(4-硝基苯基)-2-亚丙烯基]-4-氧代-2-硫代噻唑烷-3-基}丙酸(Les-45)和5-[2-氯-3-(4-硝基苯基)-2-亚丙烯基]-2-(3-羟基苯基氨基)噻唑-4(5H)-酮(Les-247)。在我们的研究中,我们分析了Les-45和Les-247对代谢活动的影响，caspase-3活性，以及与健康人成纤维细胞（BJ）和人肺癌细胞系（A549）中炎症和抗氧化防御以及细胞骨架重排相关的基因和蛋白质的表达。将细胞暴露于递增浓度（1nM至100μM）的研究化合物24小时和48小时。两种化合物在10至100μM的浓度范围内诱导BJ和A549细胞系中代谢活性的降低。两种化合物均降低了BJ细胞中NRF2（核因子红系2相关因子2）和β-肌动蛋白的mRNA表达。有趣的是,在BJ细胞系中检测到NF-κB基因和蛋白质表达水平显着降低，表明所研究的化合物对抑制炎症的直接影响。然而,由于Les-45和Les-247干扰微管蛋白/肌动蛋白细胞骨架的能力，需要更多的研究，即，真核细胞中存在的关键系统。
