BackgroundFusidic acid (FA) (WU-FA-00) is the only commercially available antimicrobial from the fusidane family that has a narrow spectrum of activity against Gram-positive bacteria.MethodsHerein, the hydrogenation derivative (WU-FA-01) of FA was prepared and both compounds were examined against a panel of six bacterial strains. In addition, their anti-inflammatory properties were evaluated using a 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model.ResultsThe results of the antimicrobial assay revealed that both WU-FA-00 and WU-FA-01 displayed a high level of antimicrobial activity against Gram-positive strains. Moreover, killing kinetic studies were performed and the results were in accordance with the minimum inhibitory concentration and minimum bactericidal concentration results. We also demonstrated that the topical application of WU-FA-00 and WU-FA-01 effectively decreased TPA-induced ear edema in a dose-dependent manner. This inhibitory effect was associated with the inhibition of TPA-induced upregulation of proinflammatory cytokines IL-1β, TNF-α, and COX-2. WU-FA-01 significantly suppressed the expression levels of p65, IκB-α, and p-IκB-α in the TPA-induced mouse ear model.ConclusionOverall, our results showed that WU-FA-00 and WU-FA-01 not only had effective antimicrobial activities in vitro, especially to the Gram-positive bacteria, but also possessed strong anti-inflammatory effects in vivo. These results provide a scientific basis for developing FA derivatives as antimicrobial and anti-inflammatory agents.

No abstract

No abstract

18Fusidic acid (WU-FA-00) is the only commercially available antimicrobial from 19 the fusidane family that has a narrow spectrum of activity against Gram-positive 20 bacteria. Herein, the hydrogenation derivative (WU-FA-01) of fusidic acid was 21 prepared, and both compounds were examined against a panel of six bacterial strains. 22In addition, their anti-inflammation properties were evaluated using a 23 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema model. The 24 results of the antimicrobial assay revealed that both WU-FA-00 and WU-FA-01 25 displayed a high level of antimicrobial activity against Gram-positive strains. 26 Moreover, killing kinetic studies were performed, and the results were in accordance 27 with the MIC and MBC results. We also demonstrated that the topical application of 28 WU-FA-00 and WU-FA-01 effectively decreased TPA-induced ear edema in a 29 dose-dependent manner. This inhibitory effect was associated with the inhibition of 30 TPA-induced up-regulation of pro-inflammation cytokines IL-1β, TNF-α and COX-2. 31 WU-FA-01 significantly suppressed the expression levels of p65, IκB-α, and p-IκB-α 32 in the TPA-induced mouse ear model. Overall, our results showed that WU-FA-00 and 33 WU-FA-01 not only had effective antimicrobial activities in vitro, especially to the 34 Gram-positive bacteria, but also possessed strong anti-inflammatory effects in vivo.35

No abstract