pogostone and Escherichia-coli-Infections

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.

Topics: Anti-Bacterial Agents; Bacteria; Drug Design; Escherichia coli; Escherichia coli Infections; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Docking Simulation; Oils, Volatile; Oxidoreductases; Staphylococcal Infections; Staphylococcus aureus

Our pervious antibacterial studies on several traditional Chinese medicines have found that Patchouli oil from Pogostemon cablin had significant antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), which has spread worldwide and infected innumerable people. In order to find the more active natural substances in Patchouli oil, one of the major components, Pogostone, was isolated and its antibacterial activity was evaluated in vitro and in vivo in this study.. In vitro test, Pogostone was screened for antimicrobial properties against 83 bacteria comprising 35 gram positive and 48 gram negative bacteria strains via the agar double dilution method. In vivo test, specific pathogen free (SPF) strain of both male and female white Kunming mice, weighing 18-22 g, were used to test the protective ability of Pogostone after being injected with the median lethal doses (MLDs) of the tested strains.. In vitro test, Pogostone could inhibit both gram negative bacteria (0.098-1 600 µg/ml) and gram positive bacteria (0.098-800 µg/ml). For Corynebacterium xerosis and some Chryseobacterium indologenes, the minimum inhibitory concentration (MIC) values of Pogostone were extremely low (<0.098 µg/ml). It was significant that Pogostone was also active against some drug-resistant bacteria like MRSA. Furthermore, Pogostone showed antibacterial activity in vivo against Escherichia coli (E. coli) and MRSA via intraperitoneal injection. Ninety percent of the mice infected with E. coil could be protected at the concentrations of 50 and 100 mg/kg, and 60% of the mice at 25 mg/kg, while the rate of protection for the mice infected with MRSA was 60% and 50% at doses of 100 and 50 mg/kg, respectively.. Pogostone could be developed as a potential antibacterial agent for clinical therapy.

Topics: Animals; Anti-Bacterial Agents; Escherichia coli; Escherichia coli Infections; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Male; Methicillin-Resistant Staphylococcus aureus; Mice; Microbial Sensitivity Tests; Oils, Volatile; Staphylococcal Infections