Antibacterial Activity of a Promising Antibacterial Agent: 22-(4-(2-(4-Nitrophenyl-piperazin-1-yl)-acetyl)-piperazin-1-yl)-22-deoxypleuromutilin.
A novel pleuromutilin derivative, 22-(4-(2-(4-nitrophenyl-piperazin-1-yl)-acetyl)-piperazin-1-yl)-22-deoxypleuromutilin (NPDM), was synthesized in our laboratory and proved excellent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). In this study, more methods were used to further study its preliminary pharmacological effect. The antibacterial efficacy and toxicity of NPDM were evaluated using tiamulin as the reference drug. The in vitro antibacterial activity study showed that NPDM is a potent bactericidal agent against MRSA that induced time-dependent growth inhibition and a concentration-dependent post-antibiotic effect (PAE). Toxicity determination showed that the cytotoxicity of NPDM was slightly higher than that of tiamulin, but the acute oral toxicity study proved that NPDM was a low-toxic compound. In an in vivo antibacterial effect study, NPDM exhibited a better therapeutic effect than tiamulin against MRSA in a mouse thigh infection model as well as a mouse systemic infection model with neutropenia. The 50% effective dose (ED50) of NPDM in a Galleria mellonella infection model was 50.53 mg/kg. The pharmacokinetic properties of NPDM were also measured, which showed that NPDM was a rapid elimination drug in mice.
['Zuo|Xiang-Yi|XY|', 'Gao|Hong|H|', 'Gao|Mei-Ling|ML|', 'Jin|Zhen|Z|', 'Tang|You-Zhi|YZ|0000-0003-2293-0287']
D000818:Animals D000900:Anti-Bacterial Agents D002460:Cell Line D004224:Diterpenes D007313:Insecta D055624:Methicillin-Resistant Staphylococcus aureus D051379:Mice D008813:Mice, Inbred ICR D008826:Microbial Sensitivity Tests D009596:Nitrophenols D000077489:Piperazine D011083:Polycyclic Compounds D051381:Rats D013203:Staphylococcal Infections
antibacterial activity pleuromutilin derivative MRSA pharmacokinetic LC-MS/MS