Abstract
Indoleamine 2, 3-dioxygenase (IDO) is the regulatory enzyme of tryptophan degrading kynurenine pathway. The overexpression of IDO, however, leads to increase concentration of kynurenine pathway metabolites, particularly the neurotoxic metabolites 3-hydroxykynurenine and quinolinic acid. Quinolinic acid recently been established as one of the key players involved in the pathogenesis of Alzheimer’s disease (AD) and depression. The present result illustrates the binding of established non-steroidal anti-inflammatory drugs against IDO enzyme using Molegro Virtual Docker software (MVD). For this purpose we have selected one structure hits of protein overly expressing in disease from protein data bank (PDB) and non-steroidal anti-inflammatory (NSAIDs) (phenylbutazone, lornoxicam and allopurinol). Docking results show that all NSAIDs fit well into the active site of IDO. Energy scores for the top ranked ligand molecule phenyl butazone -122.256 K cal/mol, lornoixacam -112.28 K cal/mol and allopurinol -84.8765 K cal/mol. It is concluded that phenylbutazone, lornoxicam and allopurinol are possible lead molecules. Present results also prooved that they are competitive inhibitors of IDO. Our study also gives an idea that peripheral anti inflammation approaches might be beneficial in the therapy of inflammation-related central nervous system diseases such as Depression and Alzheimer.
