Three-dimensional quantitative structure activity relationship (3D-QSAR) analyses were carried out on a set of 42 xanthone derivatives in order to understand their anti-alpha glucosidic activities. The studies include Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). Models with good predictive abilities were generated with the cross validated r² (r²_cv) values for CoMFA and CoMSIA being 0.580 and 0.610 respectively. The conventional r² values were 0.949 each for both CoMFA and CoMSIA models. In addition, a homology model of human alpha glucosidase was used for docking based alignment of the compounds. The most active compound then served as a template for the alignment of the remaining structures in order to align all compounds prior to QSAR studies. Further, mapping of contours onto the active site validated each other in terms of residues involved with reference to respective contours. This integrated molecular docking based alignment followed by 3D-QSAR studies should provide further insights to support structure-based design of anti-diabetic agents with improved activity profiles.

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