2. Academic Validation
  3. Novel β-Carboline Derivative ZLWH-67 Exerts Potent Anti-MRSA Activity through Multiple Mechanisms

Novel β-Carboline Derivative ZLWH-67 Exerts Potent Anti-MRSA Activity through Multiple Mechanisms

  • ACS Infect Dis. 2026 Mar 6. doi: 10.1021/acsinfecdis.5c01020.
Jiacheng Zhuang 1 2,  Junjie Lin 1,  Wenjie Liu 3,  Bolin Du 1,  XinPeng Wang 1,  Wenbo Zhang 1,  Ting Yu 4,  Wenwu Liu 5,  Xianghuan Liu 1,  Mengyu Ren 1,  Xiaoran Wang 1,  Yilin Zhang 1,  Ning Xue 1,  Jiawen Song 1,  Tianhao Jiang 1,  Hu Chen 6,  Qimou Li,  Tianming Zhong 1,  Ying Chen 1,  Zihua Xu 1,  Xi Zeng 1,  Qingchun Zhao 1
Affiliations

Affiliations

  • 1 Department of Pharmacy, General Hospital of Northern Theater Command, 110016 Shenyang, China.
  • 2 Department of Clinical Pharmacy, Shenyang Pharmaceutical University, 110016 Shenyang, China.
  • 3 College of Life and Health Sciences, Northeastern University, 110819 Shenyang, China.
  • 4 Department of Clinical Laboratory, 80th Group Army Hospital of People's Liberation Army, 261000 Weifang, China.
  • 5 Department of Pharmacy, Peking University First Hospital, Xishiku Street, Xicheng District, 100034 Beijing, China.
  • 6 Department of Clinical Laboratory, The 78th Group Army Hospital of Chinese PLA, 157000 Mudanjiang, China.
PMID: 41791934 DOI: 10.1021/acsinfecdis.5c01020
Abstract

Infections induced by methicillin-resistant Staphylococcus aureus (MRSA) are serious, highlighting the urgent need for exploring new Antibacterial agents. Here, we report a new β-carboline derivative, termed ZLWH-67, that displays potent Antibacterial activity against MRSA. ZLWH-67 exhibited bactericidal properties, low cytotoxicity and hemolytic toxicity, and good safety in vivo and was not susceptible to resistance. The potential Antibacterial mechanisms of ZLWH-67 were studied by RNA-seq analysis and verified by RT-PCR. The results indicated that ZLWH-67 might exert its effects through multiple mechanisms, including biofilm formation suppression, membrane integrity disruption, energy metabolism disturbance, oxidative stress, and DNA damage. Further mechanistic studies demonstrated that ZLWH-67 potently inhibited biofilm formation and disrupted the integrity of the cell membrane. The disruption resulted in cytoplasmic DNA leakage, increased intracellular ROS, and inhibition of DNA synthesis, ultimately accelerating Bacterial death. Notably, ZLWH-67 showed anti-MRSA efficacy in mouse skin and pneumonia Infection models, comparable to vancomycin, emphasizing the potential as a promising anti-MRSA candidate.

Keywords

DNA synthesis; MRSA; RNA-seq analysis; ZLHW-67; antibacterial mechanism.

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