Serum biochemical evaluation following administration of imidazolyl thiazolidinedione in streptozotocin-induced diabetic rats.

BACKGROUND: Diabetes mellitus represents a prominent global health concern, characterized by a rising prevalence rate. Type 2 Diabetes Mellitus (T2DM) is purported to be associated with an intricate interplay of genetic, environmental, and lifestyle factors. While some progress have been made in T2DM management, controlling associated complications remains a great challenge in medicine. OBJECTIVES: This study investigated a synthesized Imidazolyl Thiazolidinedione antidiabetic agent (PA9), focusing on serum parameters. METHODS: Streptozotocin-induced diabetic rats (n = 6) were subjected to orally treatment with PA9 (synthesized by Shakour et al. in an equal dose of a standard drug, 0.011 mmol/kg). The study conducted to measure some specific serum factors, including lipid profiles, liver and kidney enzymes, cardiac enzymes, and oxidative stress markers, both before and after treatment. RESULTS: The study findings indicated that PA9 effectively ameliorates hyperlipidemia by significantly reducing total cholesterol and triglyceride levels in serum. Additionally, PA9 demonstrated hepatoprotective effects against TZD-induced injuries, as evidenced by decreased levels of alanine transaminase and, alkaline phosphatase. In addition, PA9 also exhibited a modulatory effect on a cardiac injury marker, creatine kinase MB. Moreover, PA9 demonstrated antioxidant properties by reducing oxidative stress markers and enhancing the activities of catalase, thiol, and superoxide dismutase. CONCLUSIONS: The synthesized TZD compound (PA9) stands out as a highly promising agent for the management of diabetes. Its significant antihyperlipidemic effects, preventive influences on organ injuries, and demonstrated efficacy in reducing oxidative stress marker (SOD) make it therapeutic agent in diabetes management. This study lays the groundwork for innovative strategies in diabetes management.

Investigation of synthesized ethyl-(2-(5-arylidine-2,4-dioxothiazolidin-3-yl) acetyl) butanoate as an effective corrosion inhibitor for mild steel in 1 M HCl: A gravimetric, electrochemical, and spectroscopic study.

The corrosion inhibition effects of five concentrations (5E-5 M to 9E-5 M) of ethyl-(2-(5-arylidine-2,4-dioxothiazolidin-3-yl) acetyl) butanoate, a novel thiazolidinedione derivative code named B1, were investigated on mild steel in 1 M HCl using gravimetric analysis, electrochemical analysis and Fourier transform infrared spectroscopy. After synthesis and purification, B1 was characterized using nuclear magnetic resonance spectroscopy. All gravimetric analysis experiments were carried out at four different temperatures: 303.15 K, 313.15 K, 323.15 K and 333.15 K, achieving a maximum percentage inhibition efficiency of 92% at 303.15 K. The maximum percentage inhibition efficiency obtained from electrochemical analysis, conducted at 303.15 K, was 83%. Thermodynamic parameters such as ΔG°ads showed that B1 adsorbs onto the MS surface via a mixed type of action at lower temperatures, transitioning to exclusively chemisorption at higher temperatures.

Molecular dynamics simulations reveal the disruption mechanism of a 2,4-thiazolidinedione derivative C30 against tau hexapeptide (PHF6) oligomer.

Derivatives of 2,4-thiazolidinedione have been reported to inhibit the aggregation of tau protein, in which compound 30 (C30) not only inhibit 80% of paired helical filament 6 (PHF6) aggregation, but also inhibit K18 and full-length tau aggregation. However, its inhibitory mechanism is unclear. In this study, to investigate the effect of C30 on tau protein, all-atom molecular dynamics simulation was performed on the PHF6 oligomer with and without C30. The results show that C30 can cause significant conformational changes in the PHF6 oligomer. The nematic order parameter P2 and secondary structure analyses show that C30 destroys the ordered structure of PHF6 oligomer, reduces the content of ß-sheet structure, and transforms ß-sheet into random coil structure. By clustering analysis, it was found that C30 has four possible binding sites on the PFH6 oligomer, and the binding ability order is S1 > S2 > S4 > S3. Following a more in-depth analyses of each site, it was determined that the S1 site is the most possible binding site mainly located between layers of L1 and L3. The hydrophobic interaction is the driving force for the binding of C30 to PHF6 oligomer. In addition, L1P4_Y310, L1P5_Y310, L3P1_V309, and L3P2_V309 are key residues for C30 binding to oligomer. Moreover, π-π interaction formed by L1P4_Y310 and L1P5_Y310 with C30 and the hydrogen bonding interaction formed by C30 with L3P3_Q307 are beneficial to the combination of C30 and oligomer. The fully understanding disrupt the mechanism of 2,4-thiazolidinedione derivative on PHF6 oligomer and the identification of binding sites will help design and discover new AD inhibitors in the future.

Can algicide (the thiazolidinedione derivative TD49) truly contribute to the restoration of microbial communities?

Harmful algal blooms (HABs) are becoming a more serious ecological threat to marine environments; they not only produce toxins, resulting in the death of marine organisms, but they also adversely affect biodiversity, which is an indicator of the health of an ecosystem. Thus, to mitigate HABs, numerous studies have been conducted to develop an effective algicide, but few studies have elucidated the effect of algicides on marine environmental health. In this study, thiazolidinedione derivative 49 (TD49), which has been developed as an algicide for the dinoflagellate Heterocapsa circularisquama, was used, and we investigated changes in phytoplankton biomass (abundance, chlorophyll a, and carbon biomass) and biodiversity (diversity, evenness, and richness) following the application of TD49. To gain deeper understanding, a large-scale mesocosm (1300 L) experiment containing control and treatment with four different concentrations (0.2, 0.4, 0.6 and 1 µM) was conducted for 10 days. Based on a previous study, TD49 shows algicidal activity against H. circularisquama depending on its concentration. The phytoplankton biomass in the TD49 treatments was generally lower than that in the control due to the algicidal effect of TD49 on H. circularisquama. The biodiversity indices (e.g., the Shannon-Weaver index) in the treatments were consistently higher than those in the control before depletion of nitrite + nitrate. Interestingly, the 0.6 µM TD49 treatment had higher biodiversity indices than the high-concentration treatment (1 µM), which appeared to show a better algicidal effect. These findings suggest that mitigation of H. circularisquama blooms with TD49 treatment may enhance phytoplankton biodiversity, but treatment with excessively high concentrations can lead to harmful effects. During the study period, regardless of the control and TD49 treatments, the total biomass of phytoplankton gradually decreased from the midpoint of the experiment to the end of the experiment. This was more likely caused by the depletion of nutrients than by the toxicity of TD49.

Ability of two new thiazolidinediones to downregulate proinflammatory cytokines in peripheral blood mononuclear cells from children with asthma

Allergic asthma is a chronic, complex inflammatory disease of the airway. Despite extensive studies on the immunomodulation of T helper (Th) cell pathways (i.e., Th1 and Th2) in asthma, little is known about the effects of Th17 pathway modulation, particularly that involving peroxisome proliferator-activated receptors (PPARs). In response, two new thiazolidinedione derivatives-namely, LPSF-GQ-147 and LPSF-CR-35 were synthesized and evaluated for their immunomodulatory effects on Th17-related cytokines, including interferon γ (IFNγ), interleukin IL-6, IL-17, and IL-22 in the peripheral blood mononuclear cells of asthmatic children. Both compounds were nontoxic even at high concentrations (i.e., 100 µM). The LPSF-CR-35 compound significantly reduced the levels of IL-17A (p = .039) and IFNγ (p = .032) at 10 µM. For IL-22 and IL-6, significant reduction occurred at 100 µM (p = .039 and p = .02, respectively). Conversely, LPSF-GQ-147 did not significantly inhibit the production of the tested cytokines, the levels of all of which were more efficiently reduced by LPSF-CR-35 than methylprednisolone, the standard compound. Real-time polymerase chain reaction assay confirmed that LPSF-GQ-147 has significant PPARγ modulatory activity. Such data indicate that both LPSF-CR-35 and LPSF-GQ-147 are promising candidates as drugs for treating inflammation and asthma

The Effect of Novel Heterocyclic Compounds on Cryptococcal Biofilm.

Biofilm formation by microorganisms depends on their communication by quorum sensing, which is mediated by small diffusible signaling molecules that accumulate in the extracellular environment. During human infection, the pathogenic yeast Cryptococcus neoformans can form biofilm on medical devices, which protects the organism and increases its resistance to antifungal agents. The aim of this study was to test two novel heterocyclic compounds, S-8 (thiazolidinedione derivative, TZD) and NA-8 (succinimide derivative, SI), for their anti-biofilm activity against strains of Cryptococcus neoformans and Cryptococcus gattii. Biofilms were formed in a defined medium in 96-well polystyrene plates and 8-well micro-slides. The effect of sub-inhibitory concentrations of S-8 and NA-8 on biofilm formation was measured after 48 h by a metabolic reduction assay and by confocal laser microscopy analysis using fluorescent staining. The formation and development of cryptococcal biofilms was inhibited significantly by these compounds in concentrations below the minimum inhibitory concentration (MIC) values. These compounds may have a potential role in preventing fungal biofilm development on indwelling medical devices or even as a therapeutic measure after the establishment of biofilm.