Thiazolidinedione Derivatives Research Articles

Synthesis, Antimicrobial Evaluation, DFT, in Silico-Docking, and ADMET Investigations of Novel Chromene-based 2,4-Thiazolidinediones.

Three series of thiazolidinedione (TZD) derivatives (5a-f, 7a-f, and 9a-f) were prepared efficiently. Afterward, the synthesized candidates' antibacterial efficacy against both gram-positive and gram-negative bacteria was assessed. Compounds 7c, 7d, and 7f had values comparable to that of ampicillin, a reference antibiotic, whereas compounds 5c, 5d, and 7e exhibited the greatest values (23.0 ± 1.0, 27.7 ± 0.6, and 20.0 ± 1.0, respectively) against gram-positive bacteria (Staphylococcus aureus). The optimal structure of the produced molecules was determined by DFT computing. To assess the binding energy and elucidate the interaction between the potential candidates and different proteins, silico-docking is employed. ADMET analysis to assess the synthesized compounds' toxicity, metabolism, excretion, distribution, and absorption.

ASPECTS OF THE USE OF ANTIDIABETIC DRUGS IN PHARMACEUTICAL PRACTICE ON THE BASIS OF RATIONAL PHARMACOTHERAPY

The aim of the article. To study of the incidence of diabetes mellitus in Ukraine and to determine the prospects for the use and pharmaceutical development of antidiabetic drugs. Materials and methods. Data from the State Registers of Medicinal Products of Ukraine, of Wholesale and Retail Prices for Medicinal Products declared in Ukraine under an international non-proprietary or generic name (01.01.2024). Were used: systematic and comparative analysis, processing and synthesis, and generalization to determine the forecasted prospects. Results. In Ukraine the number of diabetes patients increased by 11% in the group of children and adolescents; in the group of elderly patients – by 12.5%, among the adult working – 20%, diabetes of the II type predominates. The trend of increase in the number of studies on the search for therapeutic alternatives for the treatment of type II diabetes and list of medicines on the pharmaceutical market has been revealed. In Ukraine drugs for oral use include APIs of the following pharmacological groups: sulfonylureas; meglitinides; biguanides; thiazolidinedione; α-glucosidase inhibitors; DPP-4 inhibitors; SGLT-2 inhibitors. Mechanism of action of the new class of oral hypoglycemic agents, approved by the FDA, consists in blocking SGLT-2 proteins from the proximal convoluted tubule in the kidney, leads to the prevention of reabsorption and excretion of the glucose molecule. This allows its use in combination with insulin and other antidiabetic drugs for the treatment of type I and II diabetes in patients of various age categories. According to the volume of clinical studies, SGLT-2 inhibitor SGLT-2 derivative gliflozin API drugs are the second largest group of antidiabetic drugs recommended for use by FDA and EMA regulatory bodies. Conclusions. The pharmaceutical development of mono and combined drugs with APIs SGLT-2 inhibitors gliflozin derivatives in combination with APIs with metformin, DPP-4 inhibitors, APIs thiazolidinedione derivatives is promising for solving the problem of diabetes treatment and prevention of complications for patients of different age groups including working population in Ukraine.

Computer aided design, synthesis and characterisation of thiazolidinedione acetic acid derivatives as brest- cancer inhibitors

The development of new anti-cancer drugs is a dynamic process that is continuously fueled, at the basic level, by the identification of new molecular targets for chemotherapeutic intervention, and, at the clinical level, by the problems (i.e. adherence, tolerability, toxicity, and virus-drug resistance) encountered with existing drugs. Thiazolidin-2,4-dione acetic acids are a class of heterocyclic compounds which possess the aforementioned pharmacophoric features. Thus several benzylidene-thiazolidin-2,4-dione compounds were designed. A total number of 12 compounds were synthesized successfully with good purity. The structures of these compounds have been confirmed by IR & Mass spectrometry. In-vitro studies of the synthesized compounds are yet to be performed & it is expected that these studies will reflect the effectiveness of these molecules as barest cancer inhibitors and will open a new dimension for the synthesis of novel anti-cancer agents. The labile structure of the synthesized compounds allows the possibility of elaborating the present work by increasing the number of derivatives & by altering the positions of substitutions on the root nucleus followed by SAR & QSAR studies. Moreover, compounds of similar nature can be designed which will lead to the synthesis of many more structural analogues.

Design, Molecular Docking, Synthesis, Anticancer activity of Thiazolidinedione derivatives

Newly designed thiazolidine-2, four-diones RD1-RD15 were synthesized, and their anticancer activities were screened against MCF-7 cancer cells. They exhibited significant activities against MCF-7 cancer cell lines. Compounds RD3 and RD9 were identified as highly potent derivatives against MCF-7 (IC50 = 6.58 and 9.15 µM, respectively). The highly effective derivatives RD1, RD9, RD6, and RD15 were also tested against VERO normal cell lines. All derivatives were evaluated for their androgen inhibitory activities and showed varying degrees of potency, with IC50 values ranging from 0.07 to 0.83 µM. Additionally, derivatives RD1, RD6, and RD15 were assessed to confirm their in vitro binding affinities for anticancer activities. Finally, docking studies were conducted to investigate their affinities and binding modes toward androgen receptors.

Synthesis, biological evaluation and molecular docking study of pyrimidine linked thiazolidinedione derivatives as potential antimicrobial and antitubercular agents

The design and development of novel antimicrobial agents are highly desired to combat the emergence of medication resistance against microorganisms that cause infections. A series of new pyrimidine-linked thiazolidinedione derivatives (5a-j) were synthesized, characterized, and their antimicrobial properties assessed in the current investigation. Here, novel pyrimidine-linked thiazolidinedione compounds were designed using the molecular hybridization approach. Elemental and spectral techniques were used to determine the structures of the synthesized hybrids. The majority of compounds showed encouraging antibacterial properties. Among the active compounds, 5g, 5i, and 5j showed 1.85, 1.15, and 1.38 times the activity of streptomycin against S. aureus, respectively, with MIC values of 6.4, 10.3, and 8.6 µM. With MIC values of 10.8, 21.9, and 15.4 µM, respectively, the compounds 5g, 5i, and 5j showed 2.14, 1.05, and 1.50 times the activity of linezolid against the methicillin-resistant S. aureus (MRSA) strain. Furthermore, when compared to the reference medications, compounds 5g, 5i, and 5j demonstrated broad-range antimicrobial efficacy against all tested strains of bacteria and fungus. Out of all the compounds that were investigated, compounds 5g, 5i, and 5j showed noteworthy anti-tubercular activity. 5g is the most effective, 1.59 times more effective than reference drug isoniazid. To anticipate the binding manner, the synthesized potent compounds were subjected to molecular docking into the active binding site of MRSA and the mycobacterial membrane protein large 3 (MmpL3) protein. The compounds 5g, 5i, and 5j may eventually serve as lead compounds in the search for antimicrobial and anti-TB therapeutic agents.

Molecular Docking Studies of Thiazolidinediones on Receptor for Advanced Glycation End Products (RAGE)

Background: Advanced glycation end products (AGE), are abnormal glycation of molecular proteins and nucleic acid, and its interaction with receptors for advanced glycation end products (RAGE) culminates in metabolic, neurodegenerative, and lifestyle disorders. Thiazolidinediones are insulin sensitizers with anti-glycation activity and are currently used clinically as anti-diabetic drugs. Research rationale: Studies show that thiazolidinediones also exhibit antioxidant and antiglycation activity; hence we proposed that this anti-glycation activity of thiazolidinedione may be due to its anti-RAGE action, thus preventing further RAGE-AGE interaction. Purpose of the study: Aim of the current study is to assess In-silico anti-RAGE activity of nine thiazolidinediones namely pioglitazone, rosiglitazone, ciglitazone, darglitazone, englitazone, netoglitazone, rivoglitazone, troglitazone and balaglitazone with RAGE. Materials and Methods: Nine thiazolidinediones namely, pioglitazone, rosiglitazone, ciglitazone, darglitazone, englitazone, netoglitazone, rivoglitazone, troglitazone and balaglitazone were downloaded from PubChem database. RAGE protein was downloaded from the PDB database. The nine thiazolidinediones were docked with RAGE protein using Auto Dock software and interaction parameters were studied. Result: All nine thiazolidinediones showed acceptable binding energy below (-8Kcal/mol) with 1-5 hydrogen bonds. Rosiglitazone exhibits the highest binding energy (-8.24Kcal/mol) with 2 hydrogen bonds for RAGE. Troglitazone exhibits the lowest binding energy (-9.95Kcal/mol) with 3 hydrogen bonds for RAGE. Conclusion: Thus our Insilco docking studies of thiazolidinedione derivatives with RAGE conclude that these nine thiazolidinedione derivatives exhibit anti-glycation activity by direct interaction with receptors of RAGE. Thus, this work warrants future preclinical studies to claim its RAGE receptor modulation activity.

Synthesis, Molecular Docking Studies and in vitro and in vivo Hypolipidemic Activity of Thiazolidinedione Derivatives

This work aimed to design, synthesize novel thiazolidinedione derivatives, which were tested for their antihyperlipidemic effects. Antihyperlipidemic activity was carried through in silico docking study for the 50 thiazolidinedione derivatives (SMI-IV-1 to 50 derivatives) in comparison with standard pioglitazone against the crystal structure of protein PPARgamma (PDB ID: 6QJ5) proteins. Based on the binding energy further, best three derivatives were selected and characterized with IR, NMR and MASS studies. Then, in vitro evaluation of each derivative's antihyperlipidemic activity was carried out by observing their effects on the reduction ability of mature 3T3-L1 adipocyte cells. These cells are susceptible to cytotoxicity because of their internal accumulation of lipids. The vitality of 3T3-L1 adipocytes was identified using the MTT assay. Finally, animal experiments were conducted in order to verify the antihyperlipidemic action of the substance in Wistar rats that had been genetically modified to develop hyperlipidemia. Initially, acute toxicity study was carried out and then based on further study was investigated. Simvastatin (4 mg/kg) was used as standard drug. All the selected three derivatives showed a reversal of the rise in blood triglycerides, cholesterol and LDL from 6 to 48 h and in VLDL from 24 h. All the derivatives showed satisfactory results but derivatives SMI-IV-23 followed by SMI-IV-4 and SMI-IV-31 were given very significant results in terms of binding energy and also in vitro, in vivo experiments. Overall, the results concluded that all the thiazolidinedione derivatives were potent against hyperlipidemic condition and among the all derivatives few derivatives were showed significant role as non-toxic and in mitigation of hyperlipidemia.

Antidiabetic potential of thiazolidinedione derivatives with efficient design, molecular docking, structural activity relationship, and biological activity: an update review (2021-2023).

Thiazolidinedione has been used successfully by medicinal chemists all over the world in the development of potent antidiabetic derivatives. The few compounds with excellent antidiabetic potency that we have identified in this review could be used as a lead for further research into additional antidiabetic mechanisms. The information provided in this review regarding the design, biological activity, structure-activity relationships, and docking studies may be useful for scientists who wish to further explore this scaffold in order to fully utilize its biological potential and develop antidiabetic agents that would overcome the limitations of currently available medications for the treatment of diabetes. This review outlines the antidiabetic potential of Thiazolidinedione-based derivatives that have been published in the year 2021- till date.

Synthesis, in-Silico studies and biological evaluation of pyrimidine based thiazolidinedione derivatives as potential anti-diabetic agent

Despite the advancements in the management of Diabetes mellitus, the design and synthesis of drug molecule which ameliorates the hyperglycemia and associated secondary complications in diabetic patients, still remains a challenge. Herein, we report the synthesis, characterization and anti-diabetic evaluation of pyrimidine-thiazolidinedione derivatives. The synthesized compounds were characterized by 1H NMR, 13C NMR, FTIR and Mass Spectroscopic analytical techniques. The in-silico ADME studies depicted that the compounds were within the permissible limits of the Lipinski’s rule of five. The compounds 6e and 6m showing the best results in OGTT were evaluated for in-vivo anti-diabetic evaluation in STZ induced diabetic rats. Administration of 6e and 6m for four weeks decreased the blood glucose levels significantly. Compound 6e (4.5 mg/kg p.o.) was the most potent compound of the series. It reduced the level of blood glucose to 145.2 ± 1.35 compared to the standard Pioglitazone (150.2 ± 1.06). Moreover, the 6e and 6m treated group did not show increase in bodyweight. The biochemical estimations showed that the levels of ALT, ASP, ALP, urea, creatinine, blood urea nitrogen, total protein and LDH restored to normal in 6e and 6m treated groups as compared to STZ control group. The histopathological studies supported the results obtained in biochemical estimations. Both the compounds did not show any toxicity. Moreover, the histopathological studies of pancreas, liver, heart and kidney revealed that the structural integrity of these tissues restored to almost normal in 6e and 6m treated groups as compared to STZ control group. Based upon these findings it can be concluded that the pyrimidine-based thiazolidinedione derivatives represent novel anti-diabetic agents with least side effects.

Discovery of Novel Thiazolidinedione-Derivatives with Multi-Modal Antidiabetic Activities In Vitro and In Silico.

Diabetes mellitus (DM) and related complications continue to exert a significant burden on health care systems globally. Although conventional pharmacological therapies are beneficial in the management of this metabolic condition, it is still necessary to seek novel potential molecules for its management. On this basis, we have synthesised and evaluated the anti-diabetic properties of four novel thiazolidinedione (TZD)-derivatives. The TZD derivatives were synthesised through the pharmacophore hybridisation strategy based on N-arylpyrrole and TZD. The resultant derivatives at different concentrations were screened against key enzymes of glucose metabolism and glucose utilisation in the liver (HEP-G2) cell line. Additionally, peroxisome proliferator-activated receptor-γ activation was performed through docking studies. Docking of these molecules against PPAR-γ predicted strong binding, similar to that of rosiglitazone. Hence, TZDD2 was able to increase glucose uptake in the liver cells as compared to the control. The enzymatic inhibition assays showed a relative inhibition activity; with all four derivatives exhibiting ≥ 50% inhibition activity in the α-amylase inhibition assay and a concentration dependent activity in the α-glucosidase inhibition assay. All four derivatives exhibited ≥30% inhibition in the aldose reductase inhibition assay, except TZDD1 at 10 µg/mL. Interestingly, TZDD3 showed a decreasing inhibition activity. In the dipeptidyl peptidase-4 inhibition assay, TZDD2 and TZDD4 exhibited ≥20% inhibition activity.

Investigation of Cardioprotective Effect of 2, 4-thiazolidinedione Derivative Using HFD-STZ Fed Rats

Abstract: Background: Myocardial infarction is a 2nd most important origin of universal death and after coronary revascularization, cardiovascular events occurs further a lot in subjects through DM: 3.5- as well as 2-fold fatality ranks correspondingly behind percutaneous coronary intervention or coronary bypass graft surgery. Objectives: The aim of an attendance research was to discover usefulness of 2, 4- thiazolidinedione derivatives lying on diabetic MI and HFD-STZ diabetic rats. Materials and Methods: In in-vivo investigation, Type-2 diabetes was elicited by higher fatty meal plus little dosage for streptozotocin and MI was provoked by LAD Coronary artery ligation model. The rats were divided into a variety of groups, including treatment groups (Composite An epalrestat, Composite B pioglitazone). And after 15 days of treatment a variety of factors were evaluated, i.e. serum glucose, total cholesterol, serum triglycerides, lipid profile antioxidant enzymes, ECG analysis, and Histopathological examination of heart were done. Results: In in-vivo investigation, levels of serum glucose, triglycerides, LDL level, LDH level, CK-MB, Troponin I, malondialdehyde (MDA), total cholesterol, infarct area, were considerably decreased in composite A and B treated animals. Whereas the HDL level, antioxidant enzymes, had drastically risen in composite, treated animals balanced to disease control rats. In ECG analysis ST elevation was restored in drug treated animals. Composite treated heart indicated mild congestion and inflammation in histopathological examination. Homogenate of drug treated animals indicated less apoptotic signals and nearer to normal animals. Conclusion: The treatment with Composite A and Composite B notably ameliorated the alterations in MI in a dose dependant manner. Keywords: 2, 4-Thiazolidinedione, Myocardial infarction, Diabetic MI, Type-2 diabetes, LAD, Macrovascular complication.

Synthesis and enzymatic inhibition effects of thiazolidinedione 3C-like protease inhibitors

The 3C-like protease (also known as Mpro) plays a key role in SARS-CoV-2 replication and has similar substrates across mutant coronaviruses, making it an ideal drug target. We synthesized 19 thiazolidinedione derivatives via the Knoevenagel condensations and Mitsunobu reactions as potential 3C-like protease inhibitors. The activity of these inhibitors is screened in vitro by employing the enzymatic screening model of 3C-like protease using fluorescence resonance energy transfer. Dithiothreitol is included in the enzymatic reaction system to avoid non-specific enzymatic inhibition. Active inhibitors with diverse activity are found in this series of compounds, and two representative inhibitors with potent inhibitory activity are highlighted.

Green Synthesis of Thiazolidine-2,4-dione Derivatives and Their Lipoxygenase Inhibition Activity With QSAR and Molecular Docking Studies.

Thiazolidinediones are five-membered, heterocyclic compounds that possess a number of pharmacological activities such as antihyperglycemic, antitumor, antiarthritic, anti-inflammatory, and antimicrobial. Conventional methods for their synthesis are often environmentally unacceptable due to the utilization of various catalysts and organic solvents. In this study, deep eutectic solvents were used in the synthesis of thiazolidinedione derivatives that acted as both solvents and catalysts. Initially, a screening of 20 choline chloride-based deep eutectic solvents for thiazolidinedione synthesis, via Knoevenagel condensation, was performed in order to find the most suitable solvent. Deep eutectic solvent, choline chloride, N-methylurea, was proven to be the best for further synthesis of 19 thiazolidinedione derivatives. Synthesized thiazolidinediones are obtained in yields from 21.49% to 90.90%. The synthesized compounds were tested for the inhibition of lipid peroxidation as well as for the inhibition of soy lipoxygenase enzyme activity. The antioxidant activity of the compounds was also determined by the ABTS and DPPH methods. Compounds showed lipoxygenase inhibition in the range from 7.7% to 76.3%. Quantitative structure–activity relationship model (R 2 = 0.88; Q 2 loo = 0.77; F = 33.69) for the inhibition of soybean lipoxygenase was obtained with descriptors Mor29m, G2u, and MAXDP. The molecular docking confirms experimentally obtained results, finding the binding affinity and interactions with the active sites of soybean LOX-3.

Peroxisome Proliferator-Activated Receptors as Superior Targets for Treating Diabetic Disease, Design Strategies - Review Article.

Thiazolidinedione (TZD), a class of drugs that are mainly used to control type 2 diabetes mellitus (T2DM), acts fundamentally as a ligand of peroxisome proliferator-activated receptors (PPARs). Besides activating pathways responsible for glycemic control by enhancing insulin sensitivity and lipid homeostasis, activating PPARs leads to exciting other pathways related to bone formation, inflammation, and cell proliferation. Unfortunately, this diverse effect of activating several pathways may show in some studies adverse health outcomes as osteological, hepatic, cardiovascular, and carcinogenic effects. Thus, a silver demand is present to find and develop new active and potent antiglycemic drugs for treating T2DM. To achieve this goal, the structure of TZD for research is considered a leading structure domain. This review will guide future research in the design of novel TZD derivatives by highlighting the general modifications conducted on the structure component of TZD scaffold affecting their potency, binding efficacy, and selectivity for the control of T2DM.

Experimental and first-principles DFT insights into the corrosion protection mechanism of carbon steel in an HCl medium by two thiazolidinedione compounds

Researchers have investigated various approaches to avoid corrosion problems in different industries in recent decades. In line with the research trend in this field, we synthesized and characterized two thiazolidinedione derivatives, namely (Z)− 5-(4-hydroxy-3-methoxybenzylidene)thiazolidine-2,4-dione (HMTZD) and (Z)− 5-(4-fluorobenzylidene)thiazolidine-2,4-dione (FTZD), and then used them as potential inhibitors for protecting the corrosion of carbon steel (CS) in 1.0 mol/L. Corrosion inhibition performances were evaluated using electrochemical techniques such as electrochemical impedance spectroscopy (EIS), potentiodynamic polarization (PDP), linear polarization resistance (LPR), and surface characterization using a scanning electron microscope (SEM). Besides, first principles Density Functional Theory (DFT) calculations were employed to investigate the potential bonding and charge transfer between inhibitor molecules and Fe(110) surface. Electrochemical results indicated that the addition of tested inhibitors to corrosive 1.0 mol/L HCl solution significantly reduced carbon steel corrosion by increasing the polarization resistance and blocking both anodic and cathodic corrosion reactions. Further, results indicated that HMTZD and FTZD are adsorption inhibitors following Langmuir adsorption isotherm. The HMTZD demonstrated an inhibition performance of 96% at 5 × 10-3 M. In addition, the morphological analysis revealed the formation of a protective barrier onto the CS surface, which reduced corrosion attack. The adsorption mechanism was further evaluated using first-principles DFT calculations, which showed that both inhibitors can form chemical bonds with Fe-atoms. Partial density of states (PDOSs) suggested that inhibitor molecules adsorbed through charge transfer between oxygen/sulfur of molecules and Fe-atoms. The outcomes from the present work are intended to encourage further exploration of thiazolidinediones in the corrosion protection of metals.

Harnessing ROS-Induced Oxidative Stress for Halting Colorectal Cancer via Thiazolidinedione-Based SOD Inhibitors.

Based on the “canonical” view of reactive oxygen species’ (ROS) contribution to carcinogenesis, ROS induce oxidative stress and promote various tumor progression events. However, tumor cells also need to defend themselves against oxidative damage. This “heresy” was supported by several recent studies underlining the role of cellular antioxidant capacity in promoting metastasis and resistance to chemotherapy. Accordingly, harnessing the ROS-induced oxidative stress via selective suppression of the cancer antioxidant defense machinery has been launched as an innovative anticancer strategy. Within this approach, pharmacological inhibition of superoxide dismutases (SODs), the first-line defense antioxidant enzymes for cancer cells, selectively kills tumor cells and circumvents their acquired resistance. Various SOD inhibitors have been introduced, of which some were tolerated in clinical trials. However, the hit SOD inhibitors belong to diverse chemical classes and lack comprehensive structure–activity relationships (SAR). Herein, we probe the potential of newly synthesized benzylidene thiazolidinedione derivatives to inhibit SOD in colorectal cancer with special emphasis on their effects on correlated antioxidant enzymes aldehyde dehydrogenase 1 (ALDH1) and glutathione peroxidase (GPx). This may possibly bring a new dawn for utilizing thiazolidinediones (TZDs) in cancer therapy through SOD inhibition mechanisms. The preliminary 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that all of the evaluated TZDs exhibited excellent safety profiles on normal human cells, recording an EC100 of up to 47.5-folds higher than that of doxorubicin. Compounds 3c, 6a, and 6e (IC50 = 4.4–4.7 μM) were superior to doxorubicin and other derivatives against Caco-2 colorectal cancer cells within their safe doses. The hit anticancer agents inhibited SOD (IC50 = 97.2–228.8 μM). Then, they were selected for further in-depth evaluation on the cellular level. The anticancer IC50 doses of 3c, 6a, and 6e diminished the antioxidant activities of SOD (by 29.7, 70.1, and 33.3%, respectively), ALDH1A (by 85.92, 95.84, and 86.48%, respectively), and GPX (by 50.17, 87.03, and 53.28%, respectively) in the treated Caco-2 cells, elevating the Caco-2 cellular content of ROS by 21.42, 7.863, and 8.986-folds, respectively. Docking simulations were conducted to display their possible binding modes and essential structural features. Also, their physicochemical parameters and pharmacokinetic profiles formulating drug-likeness were computed.

The Hypoglycemic and Hypolipidemic Effect of 5- Naphthalidin-2, 4 Thiazolidinedione derivatives in Alloxan Induced Type II Diabetic Model

Objective: The present study was undertaken to study antidiabetic and antihyperlipidemic potentials of 5- naphthalidin-2, 4-thiazolidinediones derivatives and its interaction with rosiglitazone in alloxan-induced diabetic rats. Methods: Diabetes was induced in male swiss albino rats by single intramuscular injection of alloxan (0.15 mg/Kg i.m) and NIDDM-rats received 4b, 4c or 4d (36 mg/Kg, p.o). Fasting blood glucose (FBG) levels were measured by glucose-oxidase & peroxidase reactive strips. Serum biochemical parameters such as total cholesterol (TC), triglycerides (TG), very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol were estimated. The statistical analysis of results was carried out using Student t-test and one-way analysis (ANOVA) followed by Duncan's Multiple Range Test (DMRT). Results: The results revealed that 4b, 4c and 4d showed promising results by lowering the blood glucose. Moreover, 4c compound displayed high efficiency for lowering lipid profiles compared to others. Conclusion: These results suggest that taking 5- naphthalidin-2, 4 TZD orally twice/day is a valuable treatment for Non insulin dependent diabetes mellitus (NIDDM) and hypolipidemic agent. They exert their effects through altering regulation genes in glucose and lipid metabolisms in diabetic rats.

Neurolocomotor Behavior and Oxidative Stress Markers of Thiazole and Thiazolidinedione Derivatives against Nauphoeta cinerea.

Thiazolidine compounds NJ20 {(E)-2-(2-(5-bromo-2-methoxybenzylidene)hydrazinyl)-4-(4-nitrophenyl)thiazole} and NW05 [(2-(benzo (d) (1,3) dioxol-4-ylmethylene)-N-(4-bromophenyl)-thiosemicarbazone] potentiated the effect of norfloxacin in resistant bacteria; however, there are no reports on their effects on Nauphoeta cinerea in the literature. The objective of this work was to evaluate the behavioral effects and oxidative markers of NW05 and NJ20 in lobster cockroach N. cinerea. To evaluate the behavioral study, a video tracking software was used to evaluate the locomotor points and the exploratory profile of cockroaches in the horizontal and vertical regions of a new environment. The total concentration of thiol and reduced glutathione (GSH), substances reactive to thiobarbituric acid (TBARS), free iron (II) content and mitochondrial viability were determined. The antioxidant potential was evaluated by the DPPH method. Both substances induced changes in the behavior of cockroaches, showing a significant reduction in the total distance covered and in the speed. In the cell viability test (MTT), there was a significant reduction for NJ20 (1 mM). NJ20 caused a significant increase in total levels of thiol and non-protein thiol (NPSH), although it also slightly increased the content of malondialdehyde (MDA). Both compounds (NW05 and NJ20) caused a significant reduction in the content of free iron at a concentration of 10 mM. In conclusion, the compound NJ20 caused moderate neurotoxicity (1 mM), but had good antioxidant action, while NW05 did not show toxicity or significant antioxidant activity in the model organism tested. It is desirable to carry out complementary tests related to the antioxidant prospection of these same compounds, evaluating them at different concentrations.

Thiazolidinedione Derivatives: In Silico, In Vitro, In Vivo, Antioxidant and Anti-Diabetic Evaluation.

This work aimed to synthesize a new antihyperglycemic thiazolidinedione based on the spectral data. The DFT\\B3LYP\\6-311G** level of theory was used to investigate the frontier molecular orbitals (FMOs), chemical reactivity and map the molecular electrostatic potentials (MEPs) to explain how the synthesized compounds interacted with the receptor. The molecular docking simulations into the active sites of PPAR-γ and α-amylase were performed. The in vitro potency of these compounds via α-amylase and radical scavenging were evaluated. The data revealed that compounds (4–6) have higher potency than the reference drugs. The anti-diabetic and anti-hyperlipidemic activities for thiazolidine-2,4-dione have been investigated in vivo using the alloxan-induced diabetic rat model along with the 30 days of treatment protocol. The investigated compounds didn’t show obvious reduction of blood glucose during pre-treatments compared to diabetic control, while after 30 days of treatments, the blood glucose level was lower than that of the diabetic control. Compounds (4–7) were able to regulate hyperlipidemia levels (cholesterol, triglyceride, high-density lipoproteins and low- and very-low-density lipoproteins) to nearly normal value at the 30th day.

Thiazolidinedione derivatives as novel GPR120 agonists for the treatment of type 2 diabetes

GPR120, also called FFAR4, is preferentially expressed in the intestines, and can be stimulated by long-chain free fatty acids to increase the secretion of glucagon-like peptide-1 (GLP-1) from intestinal endocrine cells. It is known that GLP-1, as an incretin, can promote the insulin secretion from pancreatic cells in a glucose-dependent manner. Therefore, GPR120 is a potential drug target to treat type 2 diabetes. In this study, thiazolidinedione derivatives were found to be novel potent GPR120 agonists. Compound 5g, with excellent agonistic activity, selectivity, and metabolic stability, improved oral glucose tolerance in normal C57BL/6 mice in a dose-dependent manner. Moreover, compound 5g exhibited anti-diabetic activity by promoting insulin secretion in diet-induced obese mice. In summary, compound 5g might be a promising drug candidate for the treatment of type 2 diabetes.