Huo Haibo, Dan Wenjia, Qin Libo, Bo Jiaxue, Zhang Xiaonan, Yang Chaofu, Bai Bianxia, Ren Jiahong, Shi Baojun, Li Jian
Department of Life Sciences, Changzhi University, Changzhi, 046011, Shanxi, China.
School of Life Science and Technology, Shandong Second Medical University, Shandong, China.
Eur J Med Chem. 2025 Feb 5;283:117187. doi: 10.1016/j.ejmech.2024.117187. Epub 2024 Dec 18.
A novel series of steroidal β-carboline quaternary ammonium derivatives (SCQADs) derived from natural cholic acid and its derivatives was designed, synthesized and biologically evaluated against four Gram-positive bacteria for the first time. Most of these derivatives exhibited promising antibacterial activity against the tested strains, particularly, compound 21g displayed strong antibacterial activity against MRSA (MIC = 0.5-1 μg/mL) with low cytotoxicity. Meanwhile, derivative 21g was able to quickly kill Gram-positive bacteria within 0.5 h without inducing bacterial resistance. Preliminary mechanistic explorations indicated that compound 21g destroyed bacterial cell membranes to exert its antibacterial effects. Moreover, 21g exhibited high in vivo efficacy and high survival protection in a mouse skin abscess model. These findings suggested that compound 21g has great potential to develop as an antibacterial agent.
设计、合成了一系列新型甾体β-咔啉季铵衍生物（SCQADs），其由天然胆酸及其衍生物衍生而来，并首次针对四种革兰氏阳性菌进行了生物学评估。这些衍生物中的大多数对测试菌株表现出有前景的抗菌活性，特别是化合物21g对耐甲氧西林金黄色葡萄球菌（MRSA）显示出较强的抗菌活性（MIC = 0.5 - 1μg/mL）且细胞毒性较低。同时，衍生物21g能够在0.5小时内快速杀死革兰氏阳性菌，且不会诱导细菌耐药性。初步的作用机制探索表明，化合物21g通过破坏细菌细胞膜发挥其抗菌作用。此外，在小鼠皮肤脓肿模型中，21g表现出高体内疗效和高生存保护作用。这些发现表明，化合物21g具有开发成为抗菌剂的巨大潜力。
