Synthesis and antioxidant potential evaluation of some new thiazolidine-4-one derivatives

Abstract

Introduction: Diabetes mellitus (DM) is a chronic metabolic disorder resulting from a defect in insulin secretion, insulin action, or both. It is a major and growing threat to global public health. It is estimated that more than 285 million people worldwide have DM and according to WHO statistics, in 2025 the number of those affected by this disease will have risen to over 380 million. There are two main categories of this disease. Type 1, diabetes mellitus (T1DM), also called insulin-dependent diabetes mellitus and Type 2, diabetes mellitus (T2DM), the noninsulin dependent diabetes mellitus. Type 2 is far more common and it is characterized by disorders in insulin secretion and insulin resistance. This type of disease accounts for 90 to 95% of all diabetic patients. Diabetes claims four million lives every year and it is a leading cause of blindness, kidney failure, heart attack, stroke and amputation. Motivation and objectives: The classical therapy of the T2DM mellitus has four categories of pharmacological agents: sulfonylureas and glinides, biguanides, thiazolidinediones and alpha-glucosidase inhibitors. In the development and progression of diabetes and its complications, it is generally accepted that the increased oxidative stress plays a key role too. Diabetes is usually accompanied by an increased production of free radicals or impaired antioxidant defences. The aim and the objectives of this study is synthesis and antioxidant potential evaluation of new benzyliden-thiazolidine-4-one derivatives as potential antidiabetic drugs. Materials and methods: Benzylidine-thiazolidin-4-one derivatives with xanthine structure were obtained in several steps. Starting from 1,3-dimethyl-xanthine by reaction with chloracetyl chloride the corresponding ester was obtained, that with hydrazine hydrate leads to the hydrazide appropriate. This intermediary by reaction with aryl isothiocyanates (phenyl-, 4-chloro-phenyl- and 4-bromo-phenyl isothiocyanate) lead to the thiosemicarbazides that are cyclised with chloracethyl chloride. In the last step the obtained thiazolidine-4-ones were condensed with benzaldehyde. The antioxidant potential of the compounds was evaluated using phosphomolybdenum method. Results: By chemical modulation of the 1,3-dimethyl-xanthine at nitrogen from 7 position, new thiazolidine-4-ones and benzylidene-thiazolidine-4-ones were synthesized. The intermediary and final compounds were purified by recrystalization and flash chromatography. In the IR spectra all functional groups were found which is an argument to confirm their structure. Conclusions: Starting from 1,3-dimethyl-xanthine new thiazolidine-4-one derivatives with xanthine structure were obtained. The compounds were physico-chemical characterized and their structure was confirmed by IR spectroscopy. The antioxidant potential was also evaluated.