Design, synthesis, and biological evaluation of carbazole derivatives as potent antibacterial agents targeting membrane function via FabH Inhibition

被引:3
作者
Chen, Chong-Hao [1 ]
Liu, Cai-Shi [1 ]
Guo, Xiao-Meng [1 ]
Tong, Jin-Peng [1 ]
Huang, Juan [1 ]
Shi, Ting-Ting [2 ]
Sun, Juan [1 ]
机构
[1] Zhejiang Univ Sci & Technol, Sch Biol & Chem Engn, Hangzhou 310023, Peoples R China
[2] Zhejiang Chinese Med Univ, Hangzhou Xixi Hosp, Dept Pharmaceut Preparat, Hangzhou 310023, Peoples R China
基金
中国国家自然科学基金;
关键词
Carbazole; FabH; Molecular docking; Antimicrobial activity; Biofilm; SYNTHASE;
D O I
10.1016/j.molstruc.2024.137891
中图分类号
O64 [物理化学(理论化学)、化学物理学];
学科分类号
070304 ; 081704 ;
摘要
This study synthesized a series of carbazole compounds and tested their antimicrobial activity. Several of the synthesized compounds demonstrated potent inhibitory effects against Gram-negative bacteria. Molecular docking simulations with the fatty acid synthesis enzyme FabH revealed their potential antimicrobial action by interfering with fatty acid synthesis. Additionally, ADMET analysis confirmed favorable pharmacokinetic properties, providing a foundation for drug development and preclinical research. Furthermore, the optimized compound 2-(9 H - Carbazol-9-yl)- N -(4-(trifluoromethoxy)phenyl)acetamide was evaluated for its inhibitory and disruptive effects on biofilms using live/dead cell staining. The results demonstrated significant inhibition and disruption of biofilms, enhancing their antimicrobial efficacy. These findings offer valuable clues for the development of new antimicrobial drugs and hold promise for addressing the challenge of antimicrobial resistance with novel therapeutic strategies.
引用
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页数:10
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