Synthesis and Biological Evaluation of Novel Fusidic Acid Derivatives as Two-in-One Agent with Potent Antibacterial and Anti-Inflammatory Activity



Tu, Borong, Cao, Nana, Zhang, Bingjie, Zheng, Wende, Li, Jiahao, Tang, Xiaowen, Su, Kaize, Li, Jinxuan, Zhang, Zhen, Yan, Zhenping
et al (show 5 more authors) (2022) Synthesis and Biological Evaluation of Novel Fusidic Acid Derivatives as Two-in-One Agent with Potent Antibacterial and Anti-Inflammatory Activity. ANTIBIOTICS-BASEL, 11 (8). 1026-.

[thumbnail of Synthesis and Biological Evaluation of Novel Fusidic Acid Derivatives as Two-in-One Agent with Potent Antibacterial and Anti.pdf] Text
Synthesis and Biological Evaluation of Novel Fusidic Acid Derivatives as Two-in-One Agent with Potent Antibacterial and Anti.pdf - Published version

Download (6MB) | Preview

Abstract

Fusidic acid (FA), a narrow-spectrum antibiotics, is highly sensitive to various Gram-positive cocci associated with skin infections. It has outstanding antibacterial effects against certain Gram-positive bacteria whilst no cross-resistance with other antibiotics. Two series of FA derivatives were synthesized and their antibacterial activities were tested. A new aromatic side-chain analog, FA-15 exhibited good antibacterial activity with MIC values in the range of 0.781-1.563 µM against three strains of Staphylococcus spp. Furthermore, through the assessment by the kinetic assay, similar characteristics of bacteriostasis by FA and its aromatic derivatives were observed. In addition, anti-inflammatory activities of FA and its aromatic derivatives were evaluated by using a 12-O-tetradecanoylphorbol-13-acetate (TPA) induced mouse ear edema model. The results also indicated that FA and its aromatic derivatives effectively reduced TPA-induced ear edema in a dose-dependent manner. Following, multiform computerized simulation, including homology modeling, molecular docking, molecular dynamic simulation and QSAR was conducted to clarify the mechanism and regularity of activities. Overall, the present work gave vital clues about structural modifications and has profound significance in deeply scouting for bioactive potentials of FA and its derivatives.

Item Type: Article
Uncontrolled Keywords: anti-inflammatory, antimicrobial, fusidic acid, molecular docking, molecular dynamic
Depositing User: Symplectic Admin
Date Deposited: 02 Nov 2022 09:13
Last Modified: 27 Feb 2023 09:13
DOI: 10.3390/antibiotics11081026
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3165951