The Biological Evaluation of Fusidic Acid and Its Hydrogenation Derivative as Antimicrobial and Anti-inflammatory Agents

Fusidic acid(WU-FA-00) is the only commercially available antimicrobial from the fusidane family that has a narrow spectrum of activity against Gram-positive bacteria. Herein, the hydrogenation derivative (WU-FA-01) of fusidic acidwas prepared, and both compounds were examined against a panel of six bacterial strains. In addition, their anti-inflammation properties were evaluated using a 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced mouse ear edema model. The 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 MIC and MBC 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 up-regulation of pro-inflammation cytokines IL-1β, TNF-α and COX-2. WU-FA-01 significantly suppressed the expression levels of p65, Iκβ-α, and p-Iκβ-α in the TPA-induced mouse ear model. Overall, 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 fusidic acidderivatives as antimicrobial and anti-inflammatory agents.