Department of Biotechnology and Cell Biology, Medical College, University of Information Technology and Management in Rzeszow, Sucharskiego 2, 35-225 Rzeszow, Poland.
Department of Pharmaceutical, Organic and Bioorganic Chemistry, Danylo Halytsky Lviv National Medical University, Pekarska 69, 79010 Lviv, Ukraine.
Int J Mol Sci. 2024 Jul 3;25(13):7329. doi: 10.3390/ijms25137329.
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 (nuclear factor erythroid 2-related factor 2) and in the BJ cells. Interestingly, a significant decrease in the level of 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.
一系列包含噻唑烷酮环中的西姆宁部分的混合分子表现出显著的抗癌和抗微生物特性。因此，我们研究的目的是评估两种基于噻唑烷酮的衍生物，即 3-{5-[(Z,2Z)-2-氯-3-(4-硝基苯基)-2-丙烯基]-4-氧代-2-噻唑啉-3-基}丙酸酸（Les-45）和 5-[2-氯-3-(4-硝基苯基）-2-丙烯基]-2-(3-羟基苯氨基)噻唑-4(5H)-酮（Les-247）的性质和作用机制。在我们的研究中，我们分析了 Les-45 和 Les-247 对代谢活性、半胱天冬酶-3 活性以及与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表达的影响，在健康人成纤维细胞（BJ）和人肺癌细胞系（A549）中。细胞暴露于研究化合物的递增浓度（1 nM 至 100 μM）24 小时和 48 小时。两种化合物在 10 至 100 μM 的浓度范围内均降低了 BJ 和 A549 细胞系的代谢活性。两种化合物均降低了 BJ 细胞中 （核因子红细胞 2 相关因子 2）和 的 mRNA 表达。有趣的是，在 BJ 细胞系中检测到 基因和蛋白质表达水平显著降低，表明研究化合物直接抑制炎症。然而，由于 Les-45 和 Les-247 能够干扰微管/肌动蛋白细胞骨架，即真核细胞中存在的关键系统，因此还需要更多的研究。
