Nitrofuran Derivatives with Benzyl Groups are Promising Candidates as Antibacterial Agents Against Staphylococcus epidermidis

• Published in: ChemistrySelect (Weinheim) 2024-08, Vol.9 (30), p.n/a
• Main Authors: Di, Fang, Peiyu, Li, Jiaoyang, Zheng, Yingying, Lai, Yanpeng, Xiong, Ruolan, Yi, Han, Deng, Zhijian, Yu, Shiqing, Han
• Format: Article
• Language: English
• Subjects: Antibacterial activity; Benzyl groups; Nitrofuran; Staphylococcus epidermidis; UTIs
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202401732

Staphylococcus epidermidis is a particular concern due to its high resistance to most antibiotics. We designed and synthesised a series of nitrofuran derivatives based on the chemical structure of nitrofurantoin. Among these derivatives, compared to nitrofurantoin, the nitrofuran derivatives with n‐alkyl groups did not effectively inhibit S. aureus with minimum inhibitory concentrations (MIC) values ranging from 16 to >128 μM, while these with benzyl groups displayed potent antibacterial activity against S. aureus with MIC values ranging from 4 to 16 μM. It suggests benzyl groups play an important role in the nitrofuran derivatives against S. aureus. The nitrofuran derivatives with benzyl groups also displayed potent antibacterial activity against S. epidermidis with MIC values ranging from 2 to 8 μM. Especially, compound 20 exhibited MIC 2 μM (0.814 μg/mL) against S. epidermidis. The CC50s of compound 20 in 293 T cells and LX‐2 cells were 3.131 μg/mL and 30.51 μg/mL, respectively. While at 128 μg/mL of compound 20, no obvious red blood cell rupture was observed. It showed minimal cytotoxicity and hemolytic activity. These findings suggest that compound 20 could function as a potential antibacterial agent for treating Urinary tract infections (UTIs) caused by S. epidermidis. Nitrofurantoin was modified as a lead compound based on the principles of drug molecular design, such as splicing of active groups, shortening and prolongation of carbon chains, changing of functional groups and so on. The nitrofuran derivatives were successfully synthesised in a SN2 process and evaluated for their antibacterial properties against the Gram‐positive and Gram‐negative bacteria.