PHARMACOPHORE MODELING AND ATOM-BASED 3D-QSAR STUDIES OF ANTIFUNGAL BENZOFURANS
Keywords:
PHASE, Ligand based pharmacophore, Atom based 3D-QSAR, Nmt InhibitorsAbstract
A novel series of benzofuran analogs was reported as nonpeptidic Myristoyl-CoA: protein N -myristoyltransferase (Nmt) inhibitors. To find out the common structural requirement of these benzofurans inhibitors, a ligand based pharmacophore and atom-based 3D-QSAR model was generated. A five-point pharmacophore model was developed with two hydrogen bond acceptors (AA), one positive ionic atom (P) and two aromatic ring residues (RR). This is denoted as AAPRR. A statistically significant 3D-QSAR model for training set of 24 compounds was obtained using this pharmacophore hypothesis with correlation coefficient (r2 = 0.916) and high Fisher ratio (F =113.9). Also, the predictive power of generated model for test set of 5 compounds was found to be significant which was confirmed by the high value of cross validated correlation coefficient (q2 = 0.804) and Pearson-R (0.917). The results of ligand based pharmacophore hypothesis and atom based 3D-QSAR model explore the detailed structural perceptivities and also highlights the important binding features of benzofurans with Nmt.
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