RT Journal Article
SR Electronic
T1 The Biological Evaluation of Fusidic Acid and Its Hydrogenation Derivative as Antimicrobial and Anti-inflammatory Agents
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 311951
DO 10.1101/311951
A1 Pan-Pan Wu
A1 Hao He
A1 W. David Hong
A1 Tong-Rong Wu
A1 Su-Qing Zhao
A1 Xi-Ping Cui
A1 Ying-Ying Zhong
A1 Dong-Li Li
A1 Xue-Tao Xu
A1 Zhao-Jun Sheng
A1 Bo-Rong Tu
A1 Min Gao
A1 Jun Zhou
A1 Stephen A. Ward
A1 Paul M. O’Neill
A1 Kun Zhang
YR 2018
UL http://biorxiv.org/content/early/2018/05/01/311951.abstract
AB 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 acid was 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, IκB-α, and p-IκB-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 acid derivatives as antimicrobial and anti-inflammatory agents.