关键词: 3-Methylcarbazole衍生物, 结构修饰, 异噁唑, 合成, 抗菌活性

Abstract: In order to obtain antibacterial candidate compounds, natural product 3-methylcarbazole was used as a hit compound for structural modification and optimization. A series of 3-methylcarbazole derivatives containing isoxazole moieties were designed and synthesized, and their structures were confirmed by 1H NMR, 13C NMR and elemental analysis. Antibacterial activity tests showed that these compounds exhibited significant activity against S. aureus, S. epidermidis and methicillin-resistant S. aureus(MRSA), with most derivatives demonstrating superior antibacterial activity compared to 3-Methylcarbazole. Among them, compound 3q was the most prominent, with minimum inhibitory concentration(MIC) values of 0.5, 1 and 2 μg·mL-1 against the three strains, respectively. Its anti-S. aureus and anti-S. epidermidis activities were comparable to those of the control drugs, while its anti-MRSA effect was significantly superior to that of the control drugs. The time–kill curve showed that compound 3q exerted rapid bactericidal activity against S. aureus throughout its entire growth cycle at 4×MIC. Molecular docking results revealed that compound 3q exhibited favorable binding interactions with the target protein GyrB. Additionally, compound 3q showed no toxicity toward mouse mononuclear macrophages. The introduction of the isoxazole moiety can enhance the antibacterial activity of 3-methylcarbazole.

Key words: 3-Methylcarbazole derivatives, Structural modification, Isoxzole, Synthesis, Antibacterial activity