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

BACKGROUND: The 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.

RESULTS: New 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, 1 H-NMR, 13 C-NMR, 19 F-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.

CONCLUSIONS: For 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.