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

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

Synthesis and biological evaluation of pentacyclic triterpenoid derivatives as potential novel antibacterial agents

“…The antimicrobial activity of were determined according to the standard agar disk diffusion method with a slight modification [38,[40][41][42]. A 0.5 McFarland (1×10 7 to 1×10 8 CFU/mL) concentration of the bacterial suspension was uniformly inoculated onto MHA solidified in 120 mm petri dishes.…”

“…The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were determined by a microdilution method in 96-well plates according to Clinical and Laboratory Standards Institute (CLSI), with a slight modification [37,38,43]. A dilution series of the triterpenoids derivatives were obtained with DMSO as the solvent by two-fold serial dilution.…”

“…In particular, compound 33 demonstrated the highest activity (MIC = 1.25 μmol/L) against all four strains within this series. The time killing kinetic studies were performed over a period of 20 hours' assay at 37 ℃ according to previously reported study with a slightly modification [35][36][37][38]. Figure 3 displayed the time-kill curves of selected GA derivatives of 21, 32 and 33 against two strains of drug sensitive Staphylococcus aureus (ATCC 6538 and ATCC 29213) and Staphylococcus epidermidis (ATCC 12228).…”

The global prevalence of fusidic acid resistance in clinical isolates of Staphylococcus aureus: a systematic review and meta-analysis

“…Fusidic acid (FA) is one of the important antibacterial agents that requires ongoingevaluation of its mode of action and assessment of its resistance rate to help improve treatment strategies, particularly in the caseof staphylococcal infections. FA, derived from the fungus Fusidium coccineum (in 1960), shows moderate activity against most Gram-positive bacteria including staphylococci and also covering methicillin-resistant S. aureus (MRSA), and some anaerobic Gram-negative organisms [ 7 ]. It is generally used topically for the treatment of S. aureus skin infections.…”

“…Different creams and ointments containing FA are commercially available. Intravenous and oral preparations of this antibiotic are also used as anti-staphylococcal agents to treat persistent skin infections as well as chronic bone and joint infections [ 7 , 8 ]. In addition, FA is an important and valuable alternative to vancomycin to combat resistant organisms [ 4 ].…”