These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Tideglusib and Its Analogues As Inhibitors of Staphylococcus aureus SrtA.
    Author: Yang T, Zhang T, Guan XN, Dong Z, Lan L, Yang S, Yang CG.
    Journal: J Med Chem; 2020 Aug 13; 63(15):8442-8457. PubMed ID: 32639734.
    Abstract:
    Sortase A (SrtA) anchors surface proteins to the cell wall envelope, and it has attracted increasing interesting as a potential antivirulence target. Several small-molecule inhibitors for SrtA have been developed, but target validation remains largely underexplored. Herein, we report a new class of SrtA inhibitors that supports antivirulence therapy through small-molecule targeting of SrtA. Tideglusib (TD), a drug candidate for myotonic dystrophy, was outstanding in high-throughput screening. A concise synthetic route quickly provided TD analogues, and the structure-activity relationships for SrtA inhibition have been established from those analogues. Several compounds largely retained the in vitro potency and exhibited a better solubility than TD. Additionally, TD attenuated virulence-related phenotypes in vitro and protected mice against lethal S. aureus USA300 bacteremia. Our study indicates that TD and its analogues could be new candidates as SrtA inhibitors with potential in the development of new antivirulence agents.
    [Abstract] [Full Text] [Related] [New Search]