Abstract：
Antimicrobial resistance (AMR) interferes with the effective treatment of infections and increases the risk of microbial spread and infection-related illness and death. The synergistic activities of combinations of antimicrobial compounds offer satisfactory approaches to some extent. Structurally diverse naphthoquinones (NQs) including menadione (-CH3 group at C2) exhibit substantial antimicrobial activities against multidrug-resistant (MDR) pathogens. We explored the combinations of menadione with antibiotic ciprofloxacin or ampicillin against Staphylococcus aureus and its biofilms. We found an additive (0.590 %) were also observed. However, preformed biofilms were not affected. Dent formation was also evident in S. aureus treated with the test compounds. The structure-function relationship (SFR) of NQs was used to determine and predict their activity pattern against pathogens. Analysis of 10 structurally distinct NQs revealed that the compounds with -Cl, -Br, -CH3 , or -OH groups displayed the lowest MICs (32-256 μg/mL). Furthermore, 1,4-NQs possessing a halogen or -CH3 moiety showed elevated ROS activity, whereas molecules with an -OH group affected cell integrity. Improved activity of antimicrobial combinations and SFR approaches are significant in antimicrobial therapies.
摘要：
抗菌素耐药性（AMR）干扰了微生物感染的有效治疗，增加了微生物传播的风险，疾病,和死亡。抗微生物剂组合的协同活性在某种程度上提供了令人满意的方法。结构多样的萘醌（NQs），包括甲萘醌（C-2-CH3），对多重耐药（MDR）病原体表现出实质性的抗菌活性。我们探索了甲萘醌与抗生素环丙沙星或氨苄西林对金黄色葡萄球菌及其生物膜的组合。我们发现甲萘醌与环丙沙星和氨苄青霉素具有相加（0.590%)。然而,预先形成的生物膜没有受到影响。在用测试化合物处理的金黄色葡萄球菌中,凹陷形成也是明显的。使用NQs的结构-功能关系（SFR）来确定和预测其针对病原体的活性模式。对10个结构不同的NQ的分析表明，具有-Cl的化合物，-Br,-CH3或-OH基团显示最低的MIC（32-256µg/mL）。此外，具有卤素或-CH3部分的1,4-NQs显示出升高的ROS活性，而具有-OH基团的分子影响细胞完整性。抗微生物组合和SFR方法的改善的活性在抗微生物疗法中是显著的。
