Journal :   Asian Journal of Research in Chemistry

Volume No. :   6

Issue No. :  11

Year :  2013

Pages :   1049-1053

ISSN Print :  0974-4169

ISSN Online :  0974-4150


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In silico Identification of Potential Xanthine Oxidase Inhibitors for the Treatment of Gout and Cardiovascular Disease

Address:   C.Buvana1, A. Sumathy1, M. Sukumar2
1Dept. of Pharmaceutical Chemistry, Grace College of Pharmacy, Palakkad-678004
2Dept. of Pharmaceutical Analysis, College of Pharmacy, Sri Ramakrishna Institute of Paramedical Sciences, Coimbatore.
*Corresponding Author

Binding interactions of drugs using docking studies is an important component of computer aided drug design. Structure-based lead optimization approaches are a major role in the drug-discovery process. XO(xanthine oxidase) is the key enzyme that catalyzes the oxidation of hypoxanthine to xanthine and then to uric acid. Hyperuricemia is an underlying cause of gout and 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. A series of indole linked with thiazolidinone were computationally designed and energy minimized. The molecular properties were calculated from suitable computational tools. These ligands were investigated for drug like properties by calculating Lipinski’s rule of five using molinspiration. All of the derivatives showed a zero violations of the rule of 5 which indicates good bioavailability. The positive bioactivity score of the derivative were also in agreement with their probability of drug likeness. These compounds were docked into the active site of XO (PDB code-1HZP) using Argus lab docking software which showed good binding energy for the enzyme, when compared with the binding energies of standard drug allopurinol (-6.91kcal/mol.) Among all the designed ligands, the ligand TZ2 and TZ4 showed more binding energy values (-10.074 and = -9.158Kcal/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. In future we planned to synthesise these ligand and to screen for their xanthine oxidase inhibitory activity.
Docking, Thiazolidinone, Gout, Xanthine oxidase, Allopurinol.
C.Buvana, A. Sumathy, M. Sukumar. In silico Identification of Potential Xanthine Oxidase Inhibitors for the Treatment of Gout and Cardiovascular Disease. Asian J. Research Chem. 6(11): November 2013; Page 1049-1053.
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