Molecular docking study of naturallyoccurring compounds as inhibitors of N-myristoyl transferase towards antifungal agents discovery

Abstract

Fungal infections currently remain as a common problem in public health. Actually, drug discovery programs are oriented to the searching for lead structures. Virtual screening and molecular docking constitute great alternatives in order tofind hit compounds. Novel infection targets can also be defined and employed together with molecular docking tools in drug discovery programs. Thus, thirty-two natural compounds were docked within the active site of N-myristoyl transferase (NMT) as antifungal enzyme target. From tested compounds, alkaloids, flavonoids, xanthones, and quinones exhibited strongest mean interaction with NMT than terpenoids, coumarins and phenolics. Particularly, affinities for one aporphine alkaloid, a prenylated flavonoid and two xanthones resulted to be comparable with thatof previously reported synthetic inhibitor. Several hydrophobic and polar contacts were demonstrated by comparing different computational tools. The present results let to establish three possible lead structures to develop antifungal drugs although subsequent SAR analyses are still required.