Thiazolidin-4-one, azetidin-2-one and 1,3,4-oxadiazole derivatives of isonicotinic acid hydrazide: synthesis and their biological evaluation

Abstract

A series of thiazolidin-4-one (2a–h; 3a–h), azetidin-2-one (4a–h) and 1,3,4-oxadiazole (5a–h) derivatives of isoninicotinic acid hydrazide (INH) were synthesized in order to obtain new compounds with potential anti-inflam­matory, analgesic, ulcerogenic and lipid peroxidation activities. The structures of the new compounds were supported by their IR, 1H-NMR and mass spectral data. All compounds were evaluated for their anti-inflammatory activity by the carrageenan-induced rat paw edema test method. Eleven of the new com­pounds, out of 32, showed very good anti-inflammatory activity in the carra­geenan-induced rat paw edema test, with significant analgesic activity in the tail immersion method together with negligible ulcerogenic action. The com­pounds, which showed less ulcerogenic action, also showed reduced malondial­dehyde content (MDA), which is one of the by-products of lipid peroxidation. The study showed that the compounds inhibited the induction of gastric mu­cosal lesions and it can be suggested from the results that their protective ef­fects may be related to inhibition of lipid peroxidation in the gastric mucosa.

Keywords

• anti-inflammatory activity
• analgesic activity
• ulcerogenic activity
• lipid peroxidation.