摘要：Inhibitors of the fungal enzyme N -myristoyltransferase (Nmt) reduce fungal growth, as this enzyme is essential for viability. We found that a newly synthesized benzothiazole derivative, (1 R ,3 S )- N -{2-[(cyclopeanthylcarbonyl) amino]-benzothiazol-6-yl}-3-[(2-naphthylmethyl) amino] cyclohexanecarboxamide (FTR1335), preferentially inhibited Candida albicans Nmt (CaNmt) in a dose-dependent manner. The 50% inhibitory concentration (IC50) for CaNmt was 0.49 n M , which was much lower than the 5400 n M IC50 for human Nmt (HsNmt1). The mode of CaNmt inhibition was competitive with the substrate peptide and non-competitive with myristoyl-CoA. Moreover, FTR1335 showed strong antifungal activity in vitro , and the minimum fungicidal concentration for C. albicans was 0.78 μ M . These results indicate that FTR1335 might represent a novel family of Nmt inhibitors with fungicidal activity.
