Design, molecular docking, synthesis of some thiazolidinone derivatives and evaluation of its xanthine oxidase inhibitory activity

Structure-based lead optimization approaches are a major role in the drug-discovery process. In the present work, lead compounds that satisfied Lipinski rule of five, drug likeness score and docking studies performed by using Argus lab 4.0. The designed compounds were evaluated for Xanthine oxidase(XO) inhibition binding ability to identify the new lead compounds by molecular docking. XO is the key enzyme that catalyzes the oxidation of hypoxanthine to xanthine and then to uric acid. Hyperuricemia is an underlying cause of gout& cardiovascular diseases. Allopurinol, a widely used XO inhibitor and commonly used drug to treat gout. However, a significant portion of the population suffers from adverse effects of allopurinol like gastrointestinal upset and skin rashes. Therefore use of allopurinol-like drugs with minimum side effects is the ideal drug of choice against gout. In this study, we report the synthesis of a series of thiazolidinone-4-one analogues as effective and a new class of XO inhibitors. TZ2 &TZ4 molecules showed good inhibition against XO, which were more potent than allopurinol based on their respective IC50 values. According to the docking study TZ2 and TZ4 identified as the lead moiety and showed best docking score (TZ2=-10.074kcal/mol, TZ4=-9.158kcal/mol) compared to that of standard drug (- 6.91kcal/mol). These results highlight the identification of a new class of XO inhibitors that have potential to be more efficacious, than allopurinol, to treat gout and against cardiovascular diseases.
Author(s): C. Buvana1, T. K Ravi and M. Sukumar

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