Topological, hydrophobicity, and other descriptors on α-glucosidase inhibition: a QSAR study on xanthone derivatives

Abstract

Quantitative structure activity relationship analysis was performed on a series of xanthone derivatives to establish the structural features required for α-glucosidase inhibitory activity. The computational and statistical analysis was performed with V life MDS (Molecular Design Suite) and Statistica software. The selected models show significant predictive power, stability, and reliability in terms of cross-validated correlation coefficient (Q²_cv > 0.74 and Q²_test > 0.5) and other validation parameters. The results show that the SaaaC count, MMFF_6 and dipole moment are mainly contributed for the activity along with the hydrophobicity descriptors. It describes that heteroatoms (oxygen atom connected with carbon atom) in the molecules are favourable for α-glucosidase inhibitory activity. The E-state count descriptor suggests that when carbon atoms connected with three aromatic bonds and hydrogen or other atoms are favourable for the activity. The SAHA and SAMH descriptors show that the hydrophilic area in the molecule is important for the activity while high hydrophilicity is unfavourable for the activity. This study concluded that hydrophilic, polar and/or electron negative groups, which are responsible for hydrogen bonding and interaction with the enzyme for favourable activity.

Keywords::

• QSAR
• xanthone derivatives
• α-glucosidase inhibitor
• electrotopological
• hydrophobicity

Acknowledgement

The authors are thankful to V Life Technologies, Pune, India for providing the softwares used in the study.

Declaration of interest

N.S.H.N.M. greatfully acknowledges the Foundation of Science and Technology (FCT), Portugal for Postdoctoral Grant (SFRH/BPD/44469/2008). The authors greatfully acknowledge FCT for providing financial support for the project PTDC/QUI/68302/2006.