title: Prediction of the relationship between the structural features of andrographolide derivatives and α-glucosidase inhibitory activity: a quantitative structure-activity relationship (QSAR) study.
abstract: In order to predict the structural features responsible for α-glucosidase inhibitory activity, a quantitative structure-activity relationship (QSAR) analysis was performed on a series of andrographolide derivatives. To determine the quantitative relationship for the statistically significant models in terms of r (>0.8), F (99%) and Q(2) (>0.71) values were selected. The promising results we obtained could be used to predict the structural requirements for the inhibition of α-glucosidase activity. The models developed included: subdivided surface area, adjacency, surface volume and shape, molecular orbital package (MOPAC) and partial charge descriptors and showed a high correlation with the inhibitory activity. The descriptors used revealed that a van der Waals (vdW) surface with significant polar volume is favourable to the activity. The positive effect of the shape descriptors; PM3-LUMO and vsurf_wp7 and the negative effect of GCUT_PEOE_2 indicated that the active site may contain some nucleophilic positions that could interact with the ligand and the hydrogen acceptor and/or donor groups for hydrogen bonding with inhibitors.
authors.affiliation: REQUIMTE, Department of Chemistry, Faculty of Sciences, University of Porto, Porto, Portugal.
authors.forename: N S Hari Narayana
authors.initials: NS
authors.lastname: Moorthy
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Ramos
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Fernandes
mesh_terms: D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D004224:Diterpenes / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D006859:Hydrogen; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D004224:Diterpenes; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; C030419:andrographolide; D006859:Hydrogen; D000520:alpha-Glucosidases