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  3. Novel steroidal β-carboline derivatives as promising antibacterial candidates against methicillin-resistant Staphylococcus aureus

Novel steroidal β-carboline derivatives as promising antibacterial candidates against methicillin-resistant Staphylococcus aureus

  • Eur J Med Chem. 2025 Feb 5:283:117187. doi: 10.1016/j.ejmech.2024.117187.
Haibo Huo 1,  Wenjia Dan 2,  Libo Qin 3,  Jiaxue Bo 1,  Xiaonan Zhang 1,  Chaofu Yang 4,  Bianxia Bai 1,  Jiahong Ren 5,  Baojun Shi 6,  Jian Li 7
Affiliations

Affiliations

  • 1 Department of Life Sciences, Changzhi University, Changzhi, 046011, Shanxi, China.
  • 2 School of Life Science and Technology, Shandong Second Medical University, Shandong, China.
  • 3 Department of Chemistry, Changzhi University, Changzhi, 046011, Shanxi, China.
  • 4 School of Pharmacy, Changzhi Medical College, Changzhi, 046000, China.
  • 5 Department of Life Sciences, Changzhi University, Changzhi, 046011, Shanxi, China. Electronic address: renjiahong76@hotmail.com.
  • 6 College of Plant Protection, Northwest A&F University, Yangling, 712100, Shaanxi, China. Electronic address: shibaojun@nwsuaf.edu.cn.
  • 7 Department of Life Sciences, Changzhi University, Changzhi, 046011, Shanxi, China; Department of Chemistry, Changzhi University, Changzhi, 046011, Shanxi, China. Electronic address: lijian3773@163.com.
PMID: 39709796 DOI: 10.1016/j.ejmech.2024.117187
Abstract

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.

Keywords

Antibacterial activity; Mechanism; Quaternary ammonium derivatives; Steroidal β-carboline.

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