Inhibitors of Aspartate Transcarbamoylase Inhibit Mycobacterium tuberculosis Growth
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15640%2F23%3A73621865" target="_blank" >RIV/61989592:15640/23:73621865 - isvavai.cz</a>
Result on the web
<a href="https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cmdc.202300279" target="_blank" >https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cmdc.202300279</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/cmdc.202300279" target="_blank" >10.1002/cmdc.202300279</a>
Alternative languages
Result language
angličtina
Original language name
Inhibitors of Aspartate Transcarbamoylase Inhibit Mycobacterium tuberculosis Growth
Original language description
Aspartate transcarbamoylase (ATCase) plays a key role in the second step of de novo pyrimidine biosynthesis in eukaryotes and has been proposed to be a target to suppress cell proliferation in E. coli, human cells and the malarial parasite. We hypothesized that a library of ATCase inhibitors developed for malarial ATCase (PfATCase) may also contain inhibitors of the tubercular ATCase and provide a similar inhibition of cellular proliferation. Of the 70 compounds screened, 10 showed single-digit micromolar inhibition in an in vitro activity assay and were tested for their effect on M. tuberculosis cell growth in culture. The most promising compound demonstrated a MIC90 of 4 & mu;M. A model of MtbATCase was generated using the experimental coordinates of PfATCase. In silico docking experiments showed this compound can occupy a similar allosteric pocket on MtbATCase to that seen on PfATCase, explaining the observed species selectivity seen for this compound series.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10401 - Organic chemistry
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
ChemMedChem
ISSN
1860-7179
e-ISSN
1860-7187
Volume of the periodical
18
Issue of the periodical within the volume
17
Country of publishing house
DE - GERMANY
Number of pages
7
Pages from-to
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UT code for WoS article
001017616800001
EID of the result in the Scopus database
2-s2.0-85163771459