Synthesis and Biological Evaluation of Some New Rhodanine Analogues as Aldose Reductase Inhibitors (ARIs)

Abstract

Diabetes mellitus is a metabolic disorder characterized by hyperglycemia resulting long-term secondary complication. Aldose reductase, the rate-limiting enzyme of the polyol pathway, plays a key role in the treatment of diabetic complications. Appropriately, inhibition of this enzyme is emerging as a major therapeutic strategy for the pathogenesis of secondary complication. In this study, we describe a series of 5 aryl benzylidene -thiazolidine, 4-dione derivatives, F3 synthesized as aldose reductase inhibitors. Besides inhibiting efficiently the target enzyme, F4 and F5 showed additional AR inhibitory as well as hypoglycaemic activity (146.15 and 175.20 mg/dl ) thus emerging as novel dual acting compounds. The bezylidene derivative F3, the most promising of the whole series, showed a well-balanced, consisting of ALR2 inhibitory efficacy (83.00% at 10µg/mL), similarly, F3 have lower blood glucose level in the range of 131.11 mg/dl at 15 mg/kg body weight. This compound show robust in vitro and in vivo efficacy, and could be considered as promising dual target antidiabetic drug candidates.
 Keywords: Diabetes mellitus, hyperglycemia, Aldose reductase inhibitors