QSAR analysis of N-myristoyltransferase inhibitors: antifungal activity of benzofurans

Benzofurans are a class of antifungal agents reported to act by selective inhibition of the N-myristoyltransferase (Nmt) enzyme in fungal cells. A three-dimensional quantitative structure–activity relationship (3D-QSAR) was performed on a series of 29 molecules to find correlation between various physicochemical descriptors and Nmt inhibition. QSAR equations were evaluated using a training set 24 molecules and an external test set of 5 molecules. The statistical quality of the QSAR models was evaluated using the parameters r2, rcv2, and the rpred2 measure. The results obtained indicated that the enzyme inhibitory activity of benzofuran analogues strongly depends on structural factors as expressed by hydrogen-bond acceptors and spatial factors as expressed by the principle moment of inertia in the X (PMI_X) and Y directions (PMI_Y).