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Published on: December 27, 2016
New Tetraphenylethylene Benzoic Acid Derivatives as Antibacterial Agents for Gram-Positive Bacteria with Ultralow
Xuefan Guo1, Yanghan Peng1, Mingge Zhang2
1State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, P. R. China.
Abstract:
The misuse of antibiotics has intensified the emergence of drug-resistant bacteria. The diversity of chemical structures offers a crucial foundation for developing novel small-molecule antibacterials. New chemical scaffolds may hold significant potential for combating drug-resistant bacteria. In this study, a series of benzoic acid derivatives featuring a tetraphenylethylene (TPE) core were designed to modulate their pKa by incorporating various electron-donating and electron-withdrawing groups. This approach led to the development of a series of effective Staphylococcus aureus therapeutic agents. Among these compounds, the nitro-substituted tetraphenylethylene benzoic acid derivative (NOA) exhibits an ultralow minimum inhibitory concentration (MIC = 0.04 μg/mL) against S. aureus, while MIC of the traditional antibiotic vancomycin was 0.13 μg/mL. NOA achieved a 99% elimination rate of S. aureus at a 0.16 μg/mL and displayed antibacterial activity against S. aureus biofilm at 0.32 μg/mL. NOA could effectively treat wound infections caused by S. aureus in infected mouse models. This study provides valuable advice about the chemical substituents for designing new antibacterial agents.
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