Maria Apotrosoaei

Synthesis and Biological Evaluation of New 1,3-Thiazolidine-4-one Derivatives of 2-(4-Isobutylphenyl)propionic Acid

New thiazolidine-4-one derivatives of 2-(4-isobutylphenyl)propionic acid (ibuprofen) have been synthesized as potential anti-inflammatory drugs. The structure of the new compounds was proved using spectral methods (FR-IR, 1H-NMR, 13C-NMR, MS). The in vitro antioxidant potential of the synthesized compounds was evaluated according to the total antioxidant activity, the DPPH and ABTS radical scavenging assays. Reactive oxygen species (ROS) and free radicals are considered to be involved in many pathological events like diabetes mellitus, neurodegenerative diseases, cancer, infections and more recently, in inflammation. It is known that overproduction of free radicals may initiate and amplify the inflammatory process via upregulation of genes involved in the production of proinflammatory cytokines and adhesion molecules. The chemical modulation of acyl hydrazones of ibuprofen 3a–l through cyclization to the corresponding thiazolidine-4-ones 4a–n led to increased antioxidant potential, as all thiazolidine-4-ones were more active than their parent acyl hydrazones and also ibuprofen. The most active compounds are the thiazolidine-4-ones 4e, m, which showed the highest DPPH radical scavenging ability, their activity being comparable with vitamin E.

Design, Synthesis and the Biological Evaluation of New 1,3-Thiazolidine-4-ones Based on the 4-Amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one Scaffold

New thiazolidine-4-one derivatives based on the 4-aminophenazone (4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one) scaffold have been synthesized as potential anti-inflammatory drugs. The pyrazoline derivatives are known especially for their antipyretic, analgesic and anti-inflammatory effects, but recently there were synthesized new compounds with important antioxidant, antiproliferative, anticancer and antidiabetic activities. The beneficial effects of these compounds are explained by nonselective inhibition of cyclooxygenase izoenzymes, but also by their potential scavenging ability for reactive oxygen and nitrogen species. The structure of the new compounds was proved using spectroscopic methods (FR-IR, 1H-NMR, 13C-NMR, MS). The in vitro antioxidant potential of the synthesized compounds was evaluated according to the ferric reducing antioxidant power, phosphomolydenum reducing antioxidant power, DPPH and ABTS radical scavenging assays. The chemical modulation of 4-aminophenazone (6) through linkage to thiazolidine-propanoic acid derivatives 5a–l led to improved antioxidant potential, all derivatives 7a–l being more active than phenazone. The most active compounds are the derivatives 7e, and 7k, which showed the higher antioxidant effect depending on the antioxidant assay considered.

Synthesis and biological evaluation of the new 1,3-dimethylxanthine derivatives with thiazolidine-4-one scaffold

BackgroundThe xanthine structure has proved to be an important scaffold in the process of developing a wide variety of biologically active molecules such as bronchodilator, hypoglycemiant, anticancer and anti-inflammatory agents. It is known that hyperglycemia generates reactive oxygen species which are involved in the progression of diabetes mellitus and its complications. Therefore, the development of new compounds with antioxidant activity could be an important therapeutic strategy against this metabolic syndrome.ResultsNew thiazolidine-4-one derivatives with xanthine structure have been synthetized as potential antidiabetic drugs. The structure of the synthesized compounds was confirmed by using spectral methods (FT-IR, 1H-NMR, 13C-NMR, 19F-NMR, HRMS). Their antioxidant activity was evaluated using in vitro assays: DPPH and ABTS radical scavenging ability and phosphomolybdenum reducing antioxidant power assay. The developed compounds showed improved antioxidant effects in comparison to the parent compound, theophylline. In the case of both series, the intermediate (5a–k) and final compounds (6a–k), the aromatic substitution, especially in para position with halogens (fluoro, chloro), methyl and methoxy groups, was associated with an increase of the antioxidant effects.ConclusionsFor several thiazolidine-4-one derivatives the antioxidant effect of was superior to that of their corresponding hydrazone derivatives. The most active compound was 6f which registered the highest radical scavenging activity.Graphical abstractDesign and synthesis of new thiazolidine-4-one derivatives.