数字农科院2.0

Synthesis, Antimicrobial Activities, and Model of Action of Novel Tetralone Derivatives Containing Aminoguanidinium Moiety

文献类型： 外文期刊

作者： Qing Jie Zhang;Yu Xi Li;Wen Bo Ge;Li Xia Bai;Xiao Xu;Ya Jun Yang;Xi Wang Liu;Jian Yong Li

作者机构：

关键词： aminoguanidine;antibacterial activity;dihydrofolate reductase;drug development;ESKAPE pathogens;in vivo antibacterial efficacy;membrane disruption;MRSA;S. aureus;structure–activity relationship;synthesis;tetralone

期刊名称： International Journal of Molecular Sciences

ISSN： 1661-6596

年卷期： 2025 年 26 卷 13 期

页码：

收录情况： SCIE（2025版）

摘要： The objectives of this study were to design, synthesize, and evaluate the antibacterial activity of a series of novel aminoguanidine-tetralone derivatives. Thirty-four new compounds were effectively synthesized through nucleophilic substitution reaction and guanidinylation reaction. Chemical structures of all the desired compounds were identified by NMR and HR-MS spectroscopy. Most of the synthesized compounds showed significant antibacterial activity against ESKAPE pathogens and clinically resistant Staphylococcus aureus (S. aureus) isolates. S. aureus is an important pathogen that has the capacity to cause a variety of diseases, including skin infections, pneumonia, and sepsis. The most active compound, 2D, showed rapid bactericidal activity against S. aureus ATCC 29213 and MRSA-2 with MIC/MBC values of 0.5/4 µg/mL and 1/4 µg/mL, respectively. The hemolytic activity and cytotoxicity of 2D was low, with HC50 and IC50(HEK 293-T) values of 50.65 µg/mL and 13.09 µg/mL, respectively. Compound 2D induced the depolarization of the bacterial membrane and disrupted bacterial membrane integrity, ultimately leading to death. Molecular docking revealed that dihydrofolate reductase (DHFR) may be a potential target for 2D. In the mouse skin abscess model caused by MRSA-2, 2D reduced the abscess volume, decreased bacterial load, and alleviated tissue pathological damage at doses of 5 and 10 mg/kg. Therefore, compound 2D may be a promising drug candidate for antibacterial purposes against S. aureus.

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