Journal of Chemical and Pharmaceutical Research (ISSN : 0975-7384)

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Original Articles: 2015 Vol: 7 Issue: 10

Pharmacophore modelling and docking studies of pyrrolidinyl pyridone and pyrazinone analogues as prolyl oligopeptidase(POP) inhibitors


Prolyl oligo peptidase (POP) is a serine endo pepti dase that hydrolyses proline containing peptides wi th less than 30 amino acid length. POP enzyme suspected to be in volved in several biological functions such as cell proliferation, differentiation, signal transduction , Parkinson’s and Alzheimer’s disease. POP inhibito rs have been developed to restore the depleted neuro peptide lev els encountered in aging or in neurodegenerative di sorders. Sequentially to understand the mechanism of action, pharmacophore analyses and docking studies were pe rformed on POP inhibitors . Five point Pharmacophore with pharmacophoric feat ures, two hydrogen bond acceptors (A), one hydrophobic group (H) and two aromatic rings (R ) was generated with considerable R 2 and Q 2 values of 0.913 and 0.652 respectively. The results obtained from t his study were used for designing of new POP inhibi tors . This study further furnishes modest information in the d evelopment and investigation of POP inhibitors.