The biological evaluation of fusidic acid and its hydrogenation derivative as antimicrobial and anti-inflammatory agents

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2018
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Abstract
The biological evaluation of fusidic acid and its hydrogenation derivative as antimicrobial and anti-inflammatory agents Pan-Pan Wu,1–3 Hao He,1,3 W David Hong,1,3–5 Tong-Rong Wu,1,3 Gui-Ying Huang,2 Ying-Ying Zhong,2 Bo-Rong Tu,1,3 Min Gao,1,3 Jun Zhou,1,3 Su-Qing Zhao,1–3 Dong-Li Li,1,3 Xue-Tao Xu,1,3 Zhao-Jun Sheng,1,3 Stephen A Ward,4 Paul M O’Neill,5 Kun Zhang1–3 1Faculty of Chemical and Environmental Engineering, Wuyi University, Jiangmen, China; 2Department of Pharmaceutical Engineering, Faculty of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou, China; 3International Healthcare Innovation Institute (Jiangmen), Jiangmen, China; 4Research Centre for Drugs and Diagnostics, Liverpool School of Tropical Medicine, Liverpool, UK; 5Department of Chemistry, University of Liverpool, UK Background: Fusidic 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.Methods: Herein, 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.Results: 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 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. Conclusion: 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 FA derivatives as antimicrobial and anti-inflammatory agents. Keywords: fusidic acid, derivative, antimicrobial, anti-inflammatory
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Authors Pan-Pan Wu;Hao He;W David Hong;Tong-Rong Wu;Gui-Ying Huang;Ying-Ying Zhong;Bo-Rong Tu;Min Gao;Jun Zhou;Su-Qing Zhao;Dong-Li Li;Xue-Tao Xu;Zhao-Jun Sheng;Stephen A Ward;Paul M O’Neill;Kun Zhang and
Journal Infection and drug resistance
Year 2018
DOI
10.2147/IDR.S176390
URL
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