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

Wu, Pan-Pan, He, Hao, Hong, W David, Wu, Tong-Rong, Huang, Gui-Ying, Zhong, Ying-Ying, Tu, Bo-Rong, Gao, Min, Zhou, Jun, Zhao, Su-Qing, Li, Dong-Li, Xu, Xue-Tao, Sheng, Zhao-Jun, Ward, Steve ORCID: https://orcid.org/0000-0003-2331-3192, O'Neill, Paul M and Zhang, Kun (2018) 'The biological evaluation of fusidic acid and its hydrogenation derivative as antimicrobial and anti-inflammatory agents.'. Infection and Drug Resistance, Vol 11, pp. 1945-1957.

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Abstract

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. 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- -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 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. 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.

Item Type:	Article
Subjects:	QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 247 Anti-inflammatory agents QW Microbiology and Immunology > Bacteria > QW 127 Gram-positive endospore forming bacteria.
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.2147/IDR.S176390
SWORD Depositor:	JISC Pubrouter
Depositing User:	Stacy Murtagh
Date Deposited:	17 Dec 2018 13:45
Last Modified:	17 Dec 2018 13:45
URI:	https://archive.lstmed.ac.uk/id/eprint/9810

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