title: 3D QSAR and docking studies of various amido and benzyl-substituted 3-amino-4-(2-cyanopyrrolidide)pyrrolidinyl analogs as DPP-IV inhibitors.
abstract: The article describes the development of a robust pharmacophore model and the investigation of structure activity relationship analysis of 3-amino-4-(2-cyanopyrrolidide)pyrrolidinyl analogs reported for DPP-IV inhibition using PHASE module of Schrodinger software. The present works also encompass molecular interaction study of 3-amino-4-(2- cyanopyrrolidide)pyrrolidinyl analogs on maestro 8.5 workstation. The Phase study module comprises the five points pharmacophore model (AAHPR.617), consisting two hydrogen bond acceptor (A), one Hydrophobic (H), one Positive(P) and one aromatic ring (R) and with discrete geometries as pharmacophoric feature. The developed pharmacophore model was used to derive a predictive atom-based 3D QSAR model. The obtained 3D QSAR model has an excellent correlation coefficient value (r2=0.9926) along with good statistical significance as shown by high Fisher ratio (F=671.7). The model also exhibits good predictive power, which is confirmed by high value of cross validated correlation coefficient (q2 = 0.7311). The QSAR model suggests that hydrophobic and aromatic characters 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, electro withdrawing character positively contributes to the DPP-IV inhibition. This study provides a set of guidelines for designing compounds with better DPP-IV inhibitory potency.
authors.affiliation: Department of Chemistry, Shrimant Madhavrao Scindia, Government Model Science College, Jhansi Road, Gwalior, Madhya Pradesh, India, PIN No. 474001. riteshagrawalip@gmail.com.
authors.forename: Ritesh
authors.initials: R
authors.lastname: Agrawal
authors.forename: Pratima
authors.initials: P
authors.lastname: Jain
authors.forename: Subodh Narayan
authors.initials: SN
authors.lastname: Dikshit
authors.forename: Sourabh
authors.initials: S
authors.lastname: Jain
mesh_terms: D016208:Databases, Factual; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000737:chemistry* / Q000378:metabolism; D008024:Ligands; D062105:Molecular Docking Simulation; D011759:Pyrrolidines / Q000737:chemistry* / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D015203:Reproducibility of Results
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D008024:Ligands; D011759:Pyrrolidines