The synthesis, hypoglycemic activity and acute toxicity of new imidazole-thiazolidines hybrid structures

V. O. Chornous, O. Ya. Melnyk, O. M. Hliebov, M. V. Tykhonenko, L. M. Sheremeta, O. K. Yarosh, O. M. Denysenko, R. V. Rodik, M. V. Vovk

Abstract


The article presents a brief description of diabetes type 2 as a disease related with carbohydrate metabolism disorder mainly caused by insulin resistance and relative insulin defi ciency. It has been noted that pathologies may appear under the action of drugs of the glitazone group; it is a major cause for systematic search for new bioactive and safe compounds with the hypoglycemic action. Considering the wide range of the biological activity of imidazole derivatives and 1,3-thiazolidine the synthesis of new hybrid structures – 5-[(1-aryl-4-chloro-1H-imidazole-5-yl)methylene]-1,3-thiazolidine-2,4-diones and their exohydrated analogues – 5-[(1-aryl-4-chloro-1H-imidazole-5-yl)methyl]-1,3-thiazolidine-2,4-diones has been carried out. A preparative suitable scheme for their obtaining has been proposed, it is based on condensation of available 1-aryl-4-chloro-5-formylimidazoles with1,3-thiazolidine-4-one and further hydrogenation of the exocyclic ylidene bond formed. The results of biomedical studies of the compounds obtained in the doses of 100, 10 and 1 mg/kg have shown that they have a strong hypoglycemic activity, which exceeds the effect of test drug pioglitazone by 55%. The acute toxicity (LD50) of 5-{[1-(4-tolyl)-4chloro-1H-imidazole-5-yl]methylene}-1,3-thiazolidine-2,4-dione is 1292.92 mg/k when injected intraperitoneally.

Keywords


4-chloro-5-formylimidazoles; 1,3-thiazolidine-4-one; imidazole-thiazolidine structure; synthesis; hypo- glycemic activity; acute toxicity

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DOI: https://doi.org/10.24959/ophcj.16.872

Abbreviated key title: Ž. org. farm. hìm.

ISSN 2518-1548 (Online), ISSN 2308-8303 (Print)