Chalcomoracin and Moracin C, New Inhibitors of Staphylococcus aureus Enoyl-Acyl Carrier Protein Reductase from Morus alba

Bacterial enoyl-acyl carrier protein (ACP) reductase has been confirmed as a novel target for antibacterial drug development. In the screening of inhibitors of Staphylococcus aureus enoyl-ACP reductase (FabI), we found that a methanol extract of leaves of Morus alba L. potently inhibited S. aureus FabI as well as growth of S. aureus. The active principles were identified as chalcomoracin and moracin C by MS and NMR analysis. Chalcomoracin and moracin C inhibited S. aureus FabI with IC50 of 5.5 and 83.8 mu M, respectively. They also prevented the growth of S. aureus with minimum inhibitory concentration (MIC) of 4 and 32 mu g/mL, respectively. Consistent with their inhibition against FabI and bacterial growth, they prevented [C-14]-acetate incorporation into fatty acid in S. aureus while didn't affect protein synthesis. In this study, we reported that chalcomoracin and moracin C, potent antibacterial compounds from Morus alba, inhibited FabI and fatty acid synthesis.