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Thiazolidinones: Synthesis, Reactivity, and Their Biological Applications

Thiazolidinone is a biologically important five-membered heterocyclic ring having almost all types of biological activities. This review covers various types of thiazolidinones, such as 2-thiazolidinones, 4-thiazolidinones, 5-thiazolidinones, 2-thioxo-4-thiazolidinones, and thiazolidiene-2,4-dione. The literature related to the physical properties, chemical reactions, and synthesis for these derivatives has been included. Recent advances in the biological activities reported for 4-thiazolidinone derivatives, such as peroxisome proliferator-activated receptor gamma binders, follicle-stimulating hormone agonists, cystic fibrosis transmembrane conductance regulator inhibitors, and antioxidants, have been covered in this review. Thus, this study may help in further optimizing these thiazolidinone derivatives as more effective drug agents.

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Hybridized quinoline derivatives as anticancer agents: Design, synthesis, biological evaluation and molecular docking

Objective: Conjugating quinolones with different bioactive pharmacophores to obtain potent anticancer active agents. Methods: Fused pyrazolopyrimidoquinolines 3a-d, Schiff bases 5, 6a-e, two hybridized systems: pyrazolochromenquinoline 7 and pyrazolothiazolidinquinoline 8, different substituted thiazoloquinolines 13-15 and thiazolo[3,2-a]pyridine derivatives 16a-c were synthesized. Their chemical structures were characterized through spectral and elemental analysis, cytotoxic activity on five cancer cell lines, caspase-3 activation, tubulin polymerization inhibition and cell cycle analysis were evaluated. Results: Four compounds 3b, 3d, 8 and 13 showed potent activity than doxorubicin on HCT116 and three compounds 3b, 3d and 8 on HEPG2. These promising derivatives showed increase in the level of caspase-3. The trifloromethylphenyl derivatives of pyrazolopyrimidoquinolines 3b and 3d showed considerable tubulin polymerization inhibitory activity. Both compounds arrested cell cycle at G2/M phase and induced apoptosis. Conclusion: Compounds 3b and 3d can be considered as promising anticancer active agents with 70% of colchicine activity on tubulin polymerization inhibition and represent hopeful leads that deserve further investigation and optimization.

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Synthesis and evaluation of anticonvulsant activities of 5-benzylidene-2-(5-methylisoxazol-3-ylimino)thiazolidin-4-one derivatives

Fifteen new 5-benzylidene-2-(5-methylisoxazol-3-ylimino)thiazolidin-4-one derivatives (4-18) were synthesized and evaluated for their preliminary anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES) and rotarod tests. The structures of synthesized compounds were established by IR,1H NMR,13C NMR and mass spectral data. Among the compounds studied, 5-(3-fluorobenzylidene)-2-(5-methylisoxazol-3-ylimino)thiazolidin-4-one (8) was the most potent compound, with a median effective dose of 43.9 mg/kg and a high protective index (PI) of more than 11.1 after intraperitoneal administration in mice. Compound 8 showed significant oral activity against MES-induced seizures in mice, with an ED50 of 84.2 mg/kg and a PI above 11.8. These results demonstrate that compound 8 is safer than the commercially drugs.

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Amines having secondary aliphatic amino groups

The present invention relates to novel amides having secondary amino groups, a process for preparing them, adducts of these amines and their uses. The amides can be prepared in a simple way from readily available starting materials. They and their adducts have, in particular, a low viscosity and are suitable as constituent of polyurethane and polyurea compositions having excellent processability and high flexibility, and also as constituent of epoxy resin compositions, in particular coatings.

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PTP1b inhibition, a promising approach for the treatment of diabetes type II

Background: Diabetes Mellitus (DM), is a metabolic disorder characterized by high blood glucose levels. The main types of diabetes mellitus are Diabetes mellitus type I, Diabetes mellitus type II, gestational diabetes and Diabetes of other etiology. Diabetes type II, the Non Insulin Dependent Type (NIDDM) is the most common type, characterized by the impairment in activation of the intracellular mechanism leading to the insertion and usage of glucose after interaction of insulin with its receptor, known as insulin resistance. Although, a number of drugs have been developed for the treatment of diabetes type II, their ability to reduce blood glucose levels is limited, while several side effects are also observed. Furthermore, none of the market drugs targets the enhancement of the action of the intracellular part of insulin receptor or recuperation of the glucose transport mechanism in GLUT4 dependent cells. The Protein Tyrosine Phosphatase (PTP1b) is the main enzyme involved in insulin receptor desensitization and has become a drug target for the treatment of Diabetes type II. Several PTP1b inhibitors have already been found, interacting with the binding site of the enzyme, surrounding the catalytic amino acid Cys215 and the neighboring area or with the allosteric site of the enzyme, placed at a distance of 20 A from the active site, around Phe280. However, the research continues for finding more potent inhibitors with increased cell permeability and specificity. Objective: The aim of this review is to show the attempts made in developing of Protein Tyrosine Phosphatase (PTP1b) inhibitors with high potency, selectivity and bioavailability and to sum up the indications for favorable structural characteristics of effective PTP1b inhibitors. Methods: The methods used include a literature survey and the use of Protein Structure Databanks such as PuBMed Structure and RCSB and the tools they provide. Conclusion: The research for finding PTP1b inhibitors started with the design of molecules mimicking the Tyrosine substrate of the enzyme. The study revealed that an aromatic ring connected to a polar group, which preferably enables hydrogen bond formation, is the minimum requirement for small inhibitors binding to the active site surrounding Cys215. Molecules bearing two hydrogen bond donor/acceptor (Hb d/a) groups at a distance of 8.5-11.5 A may form more stable complexes, interacting simultaneously with a secondary area A2. Longer molecules with two Hb d/a groups at a distance of 17 A or 19 A may enable additional interactions with secondary sites (B and C) that confer stability as well as specificity. An aromatic ring linked to polar or Hb d/a moieties is also required for allosteric inhibitors. A lower distance between Hb d/a moieties, around 7.5 A may favor allosteric interaction. Permanent inhibition of the enzyme by oxidation of the catalytic Cys215 has also been referred. Moreover, covalent modification of Cys121, placed near but not inside the catalytic pocket has been associated with permanent inhibition of the enzyme.

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Synthesis and biological evaluation of indole-2-carbohydrazides and thiazolidinyl-indole-2-carboxamides as potent tubulin polymerization inhibitors

A new series of N?-(substituted phenyl)-5-chloro/iodo-3-phenyl-1H-indole-2-carbohydrazide (5, 6) and N-[2-(substituted phenyl)-4-oxo-1,3-thiazolidin-3-yl]-5-iodo/chloro-3-phenyl-1H-indole-2-carboxamide (7, 8) derivatives were synthesized and evaluated for their anticancer properties. Compounds 5a and 6b, selected as prototypes by the National Cancer Institute for screening against the full panel of 60 human tumor cell lines at a minimum of five concentrations at 10-fold dilutions, demonstrated remarkable antiproliferative activity against leukemia, non-small cell lung cancer, colon cancer, central nervous system (CNS) cancer, melanoma, ovarian cancer, renal cancer, and breast cancer (MCF-7) cell lines with GI50 values < 0.4 muM. A subset of the compounds was then tested for their potential to inhibit tubulin polymerization. Compounds 6f and 6g showed significant cytotoxicity at the nM level on MCF-7 cells and exhibited significant inhibitory activity on tubulin assembly and colchicine binding at about the same level as combretastatin A-4. Finally, docking calculations were performed to identify the binding mode of these compounds. Group 5 and 6 compounds interacted with the colchicine binding site through hydrophobic interactions similar to those of colchicine. These compounds with antiproliferative activity at high nanomolar concentration can serve as scaffolds for the design of novel microtubule targeting agents. The proportionality constant is the rate constant for the particular unimolecular reaction. the reaction rate is directly proportional to the concentration of the reactant. I hope my blog about 2682-49-7 is helpful to your research. Synthetic Route of 2682-49-7

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In heterogeneous catalysis, the catalyst is in a different phase from the reactants. Computed Properties of C3H5NOS, At least one of the reactants interacts with the solid surface in a physical process called adsorption in such a way. 2682-49-7, name is Thiazolidin-2-one. In an article£¬Which mentioned a new discovery about 2682-49-7

Studies on inclusion complexes of 2-[4-(5′-benzylidene-4′-oxo-3′-phenyl thiazolidinyl-2′-imino)benzoyl]aminoimino-5-benzylidene-3-phenyl-4-thiazolidinone with ss-cyclodextrin

Thiazolidinones and its derivatives are good pharamacores and showing wide spectrum of fungicidal, antibacterial and tubercolostic activities.A series of 2-[4-(5′-benzylidene-4′-oxo-3′-phenylthiazolidinyl-2′-imino) benzoyl] aminoimino-5-benzylidene-3-phenyl-4-thiazolidinone have been synthesized starting from p-Aminobenzoic acid.To enhance the solubility of these synthesized compounds,the inclusion complexes were prepared with ss-cyclodextrin.The synthesis of compounds and their inclusion complexes have been ascertained from the changes in spectral characteristics and their analytical data.

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Synthesis and Biological Evaluation of Novel 5-Oxo-1-Phenylpyrrolidine-3-Carboxylic Acid Analogs

A number of 5-oxo-1-phenyl-4-(substituted methyl) pyrrolidine-3-carboxylic acid derivatives bearing pyrrolidine ring and methylamino residues in their structure were synthesized as potential antibacterial drugs. The chemical structures of all the compounds were established by their UV-Vis absorption spectroscopy, IR, 1 H, 13 C NMR and mass spectroscopy. The in vitro antibacterial screening of all novel compounds was done against gram-positive Staphylococcus aureus, Bacillus subtilis and gram-negative Pseudomonas aeruginosa. The results revealed that compounds 5d, e, f and g showed moderate to good activity against the tested microbes.

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A hydrogen peroxide responsive prodrug of Keap1-Nrf2 inhibitor for improving oral absorption and selective activation in inflammatory conditions

Transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2) and its negative regulator, the E3 ligase adaptor Kelch-like ECH-associated protein 1 (Keap1), control the redox and metabolic homeostasis and oxidative stress. Inhibitors of Keap1-Nrf2 interaction are promising in oxidative stress related inflammatory diseases but now hit hurdles. By utilizing thiazolidinone moiety to shield the key carboxyl pharmacophore in Keap1-Nrf2 inhibitor, a hydrogen peroxide (H2O2)-responsive prodrug pro2 was developed. The prodrug modification improved the physicochemical properties and cell membrane permeability of the parent drug. Pro2 was stable and stayed inactive under various physiological conditions, while became active by stimulation of H2O2 or inflammation derived reactive oxygen species. Moreover, pro2 exhibited proper pharmacokinetic profile suitable for oral administration and enhanced anti-inflammatory efficiency in vivo. Thus, this novel prodrug approach may not only provide an important advance in the therapy of chronic inflammatory diseases with high level of H2O2, but also offer a fresh solution to improve the drug-like and selectivity issues of Keap1-Nrf2 inhibitors.

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Assessment of the Production of Value-Added Chemical Compounds from Sewage Sludge Pyrolysis Liquids

A procedure to analyze sewage sludge (SS) pyrolysis liquids based on solvent fractionation has been developed. Pyrolysis liquids are separated into three different fractions: heptane soluble (Hep-sol), dichloromethane soluble (DCM-sol), and hydrochloric acid soluble (HCl-sol). Diverse techniques (GC-MS, UPLC-TOF-MS) were employed to qualitatively and quantitatively analyze liquid fractions to assess the potential production of value-added chemicals. Aliphatic hydrocarbons, aliphatic nitriles, and steroids were mostly separated in the Hep-sol fraction, phenols and fatty acids in the DCM-sol fraction, and carboxylic acids and amides in the HCl-sol fraction. The largest production was obtained for ammonia (10?14 kg per tonne of SS) and alpha-olefins (8?9 kg per tonne of SS). The potential production of some of these value-added chemicals from SS pyrolysis liquid was compared with their current European production. In the case of alpha-olefins, 16 % of their European production could be achieved by SS pyrolysis.

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