The functionality of redox metabolism is frequently named as an important contributor to the processes of aging and anti-aging. Excessive activation of free radical reactions accompanied by the inability of the antioxidant defense (AOD) mechanisms to control the flow of the reactive oxygen species (ROS) leads to the persistence of oxidative stress, hypoxia, impaired mitochondrial energy function and reduced ATP potential. From a long-term perspective, such changes contribute to the development of chronic diseases and facilitate aging. In turn, preconditioning of a biosystem with small doses of stressful stimuli might cause mobilization of the mechanisms of AOD and control an excessive flow of ROS, which supports optimal functioning of the redox reactions. Those mechanisms are of crucial importance for anti-aging and are also known as a eustress or hormetic response. To ensure continuous support of mild pro-oxidant activity in a metabolic system, close monitoring and timely corrections preventing the development of excessive ROS production are required. The paper introduces the potential of heart rate variability (HRV) as a biomarker of functional and metabolic reserves and a tool to measure stress resilience during aging. The practical approaches to interpretation of HRV are provided based on total power, changes in total power in response to an orthostatic test and activities of all spectral components. It is suggested that the complex of those parameters can reflect the
depth of oxidative stress and may be used to guide lifestyle interventions and promote active longevity.
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.
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
Aim. Study of antioxidant (antiradical) activity of 6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine derivatives. Methods. In vitro study of antiradical/scavenging activity using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals inhibition assay; IC50 values determination. Results. The series of 29 modified derivatives of 6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine were evaluated
for their ability to scavenge DPPH radicals in conditions close to physiological at 5 mM concentration, and the IC50 values were determined for the most promising compounds using the serial dilutions method. The structure - antiradical activity correlations were performed and possible mechanisms of action were discussed. Conclusions. Tested 6,7-dihydro-5Himidazo[2,1-b][1,3]thiazine derivatives possess a moderate level of antiradical/scavenging activity.