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 Q² (>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.

Keywords::

• α-glucosidase inhibitory activity
• andrographolide
• Volsurf
• QSAR
• Petitjean

Acknowledgements

One of the authors N.S.H.N. Moorthy is grateful to the Fundaçao para a Ciencia e Tecnologia (FCT), Portugal, for a Postdoctoral Grant (SFRH/BPD/44469/2008).

Declaration of interest

The authors gratefully acknowledge FCT for financial support for project PTDC/QUI/68302/2006. The authors report no declarations of interests. The authors alone are responsible for the content and writing of the paper.