2. Academic Validation
  3. Discovery of novel Thymol-TPP antibiotics that eradicate MRSA persisters

Discovery of novel Thymol-TPP antibiotics that eradicate MRSA persisters

  • Eur J Med Chem. 2024 Apr 15:270:116381. doi: 10.1016/j.ejmech.2024.116381.
Ziyi Tang 1,  Jizhou Feng 2,  Mahesh Challa 2,  Sankara Rao Rowthu 2,  Shuxin Xiong 2,  Cheng Zou 2,  Jianguo Li 3,  Chandra Shekhar Verma 4,  Haibo Peng 5,  Xiaoli He 1,  Chao Huang 6,  Yun He 7
Affiliations

Affiliations

  • 1 Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China.
  • 2 Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, China.
  • 3 Singapore Eye Research Institute, Singapore, 169856, Singapore; Bioinformatics Institute, A*STAR, 30 Biopolis Street, Matrix, 138671, Singapore.
  • 4 Bioinformatics Institute, A*STAR, 30 Biopolis Street, Matrix, 138671, Singapore; Department of Biological Sciences, National University of Singapore, 117543, Singapore; School of Biological Sciences, Nanyang Technological University, 637551, Singapore.
  • 5 Chongqing Academy of Science and Technology, Chongqing, 401123, China.
  • 6 Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, China. Electronic address: chuang@cqu.edu.cn.
  • 7 Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, School of Pharmaceutical Sciences, Chongqing University, Chongqing, 401331, China; BayRay Innovation Center, Shenzhen Bay Laboratory, Shenzhen, 518132, China. Electronic address: yun.he@cqu.edu.cn.
PMID: 38604097 DOI: 10.1016/j.ejmech.2024.116381
Abstract

The high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) strains and the formation of non-growing, dormant "persisters" subsets help bacteria evade Antibiotic treatment and enhance Bacterial resistance, which poses a serious threat to human life and health. It is urgent to discover novel Antibacterial therapies effective against MRSA persisters. Thymol is a common nutraceutical with weak Antibacterial and antitumor activities. A series of Thymol triphenylphosphine (TPP) conjugates (TPP-Thy3) was designed and synthesized. These compounds showed significantly improved inhibitory activity against Gram-positive bacteria compared with Thymol. Among them, Thy3d displayed a low probability of Resistance Selection and showed excellent biocompatibility. Interestingly, Thy3d elicited a rapid killing effect of MRSA persisters (99.999%) at high concentration. Fluorescence experiments, electron microscopy, molecular dynamics simulation and bilayer experiment confirmed that Thy3d conjugates exerted potent antimicrobial activity by disrupting the integrity of the membrane of Bacterial even the persister. Furthermore, Thy3d exhibited considerable efficacy in a mouse model of subcutaneous murine MRSA Infection. In summary, TPP-Thy3 conjugates are a series of novel Antibacterial agents and could serve as a new therapeutic strategy for combating Antibiotic resistance.

Keywords

Antibacterial; Persister; Thymol; Triphenylphosphonium (TPP)-conjugates.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z