Atom-based 3D-QSAR and Docking Studies of Various 3-aminomethyl- 1,2-dihydro-4-phenyl-1-isoquinolones Derivatives as an Effective DPP-IV Inhibitors and its Validation

Author(s): Ritesh Agrawal , Pratima Jain , Subodh Narayan Dikshit , Sourabh Jain , Radhe Shyam Bahare .

Journal Name: Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Under Re-organization)

Volume 13 , Issue 3 , 2013


The article describes development of a robust pharmacophore model and investigates structure activity relationship of 3-aminomethyl-1,2-dihydro-4-phenyl-1-isoquinolone derivatives reported for DPP-IV inhibition, using PHASE module of Schrodinger software. Instant study also elaborates molecular interaction studies of 3-aminomethyl- 1,2-dihydro-4-phenyl-1-isoquinolones derivatives on maestro 8.5 workstation. The 3D-QSAR study comprises, four point pharmacophore features (APRR.9), including one hydrogen bond acceptor (A), one Positive (P) and two aromatic ring (R) with discrete geometries. The developed pharmacophore features were used to derive a predictive atom-based 3D QSAR model. Thus obtained 3D QSAR model has an excellent regression coefficient value (r2=0.9707) along with good statistical significance as shown by high Fisher ratio (F=215). The model also exhibits good predictive power, which is confirmed by high value of cross validated correlation coefficient (q2 = 0.901). The instant studied QSAR model suggests that hydrogen bond acceptor and aromatic character features are crucial for the DPP-IV inhibitory activity. The QSAR model also suggests that the inclusion of hydrophobic substituents, would enhance the DPP-IV inhibition. In addition to the hydrogen bond acceptor, hydrophobic character, electron withdrawing character features positively contribute to the DPP-IV inhibition.

Keywords: 3-amino-4-(2-cyanopyrrolidide)pyrrolidinyl analogs, docking, DPP-IV inhibitors, maestro, optimum polarized ligand simulation-2005 (OPLS-2005), pharmacophore, PHASE, QSAR, schrodinger.

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Article Details

Year: 2013
Page: [221 - 231]
Pages: 11
DOI: 10.2174/18715222113136660008
Price: $58

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