Drug design based on pentaerythritol tetranitrate reductase: synthesis and antibacterial activity of Pogostone derivatives.

Our previous work showed that Pogostone exerts antibacterial effects by targeting pentaerythritol tetranitrate reductase (PETNR). In order to develop derivatives of Pogostone with potent antibacterial activity, we performed molecular docking studies of Pogostone with PETNR and analyzed structure-activity relationships, which guided the structure design and the subsequent facile organocatalytic synthesis of Pogostone derivatives under mild reaction conditions. Several of the synthesized compounds showed antibacterial activity in vitro, including one compound (3h) that was highly effective against methicillin-resistant Staphylococcus aureus. These results suggest that Pogostone derivatives bearing functional groups on the side chain may be good leads for antibacterial drug development.