Quantitative structure–activity relationship studies have been performed on twenty one β-carboline derivatives
to investigate the structural requirements for antitumor activity. The best 2D-QSAR model (r2 = 0.802, F = 24.321, r2se =
0.325) indicated statistical significance and internal predictivity of the developed model shown by the value of cross validated
squared correlation coefficient which was 0.724. A five-point pharmacophore hypothesis yielded ligand based
pharmacophore 3D-QSAR models with good partial least-square (PLS) statistics results. The training set and test set correlation
was characterized by PLS factors (r 2 = 0.842, SD = 0.306, F = 21.3, P = 4.27e -05, Q2
ext = 0.748, RMSE = 0.531,
Pearson-R = 0.975). A docking study revealed the binding orientations of DNA intercalates at active site of amino acid
residues. The results of 2D-QSAR and 3D-QSAR give detailed structural insights and at the same time highlight the important
binding features of novel β-carboline derivatives as antitumor agents.
Keywords: β-carboline, Antitumor, Pharmacophore, 2D-QSAR, 3D-QSAR, Docking.
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