Design of Novel N-Myristoyltransferase Inhibitors of Leishmania donovani Using Four-Dimensional Quantitative Structure-Activity Relationship Analysis

Abstract

N-Myristoylation protein is catalyzed by N-myristoyltransferase (NMT), an essential target in Leishmania donovani, the causative agent of kala-azar. Four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis was applied to a series of 77 Leishmania donovani NMT inhibitors. Then, three new compounds were proposed using QSAR models. In addition, molecular docking was performed to predict the binding affinities and interaction modes among the proposed compounds and the NMT active site. In silico absorption, distribution, metabolism and excretion (ADME) evaluation was performed and potential inhibitors demonstrated satisfactory pharmacokinetic properties.