Evidence map›Paper›PMID 40221595›Full record

Articlenpj antimicrobials and resistance2025

Design, synthesis and optimization of TarO inhibitors as multifunctional antibiotics against Methicillin-resistant Staphylococcus aureus.

Yuanchen Zhong, Feifei Chen, Dianyan Chen, Qian He, Xiaofei Zhang, Lefu Lan, Chunhao Yang

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in npj antimicrobials and resistance, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Yuanchen Zhong *School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 310024, Hangzhou, China.
Feifei Chen *School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 310024, Hangzhou, China.
Dianyan ChenSchool of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 310024, Hangzhou, China.
Qian HeState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, 201203, Shanghai, China.
Xiaofei ZhangState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, 201203, Shanghai, China. xiaofeizhang@simm.ac.cn.
Lefu LanSchool of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 310024, Hangzhou, China. llan@ucas.ac.cn.
Chunhao YangState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, 201203, Shanghai, China. chyang@simm.ac.cn.

Funding

National Key Research and Development Program of China 2023YFD1800100Research Funds of Hangzhou Institute for Advanced Study, UCAS 2023HIAS-V006Shanghai Frontiers Science Center of Drug Target Identification and Delivery, Shanghai Jiao Tong University ZXWH2170101
6 · The paper itself

Abstract

UDP-N-acetylglucosamine-undecaprenyl-phosphate N-acetylglucosaminephosphotransferase (TarO) has been found to simultaneously contribute to β-lactam resistance and virulence of Methicillin-resistant Staphylococcus aureus (MRSA). However, optimization of hit compounds targeting TarO has been hindered due to their high lipophilicity and the poor correlation between the enzyme activity inhibition and β-lactam sensitization. In this study, 31 analogues of Tarocin A were designed, synthesized and evaluated by a luminescence-based reporter preliminary screening. In the subsequent β-lactams synergy test, a good correlation was observed between the results obtained from these two methods. Finally, analog 18a with more potential against TarO and an improved hydrophilicity (clogP = 3.2) was obtained. Compared with Tarocin A, 18a shows stronger β-lactam sensitizing and anti-biofilm activities in vitro, as well as potent anti-virulence and synergistic potency with imipenem in vivo. These results suggest that TarO is a promising target for combating MRSA, and 18a can serve as a lead molecule.

Identifiers

PMID40221595
PMCPMC11993615

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.