Discovery of a potent and selective human AC2 inhibitor based on 7-deazapurine analogues of adefovir
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F23%3A00577921" target="_blank" >RIV/61388963:_____/23:00577921 - isvavai.cz</a>
Alternative codes found
RIV/60461373:22310/23:43927428
Result on the web
<a href="https://doi.org/10.1016/j.bmc.2023.117508" target="_blank" >https://doi.org/10.1016/j.bmc.2023.117508</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bmc.2023.117508" target="_blank" >10.1016/j.bmc.2023.117508</a>
Alternative languages
Result language
angličtina
Original language name
Discovery of a potent and selective human AC2 inhibitor based on 7-deazapurine analogues of adefovir
Original language description
Adefovir based acyclic nucleoside phosphonates were previously shown to modulate bacterial and, to a certain extent, human adenylate cyclases (mACs). In this work, a series of 24 novel 7-substituted 7-deazaadefovir analogues were synthesized in the form of prodrugs. Twelve analogues were single-digit micromolar inhibitors of Bordetella pertussis adenylate cyclase toxin with no cytotoxicity to J774A.1 macrophages. In HEK293 cell-based assays, compound 14 was identified as a potent (IC50 = 4.45 μM), non-toxic, and selective mAC2 inhibitor (vs. mAC1 and mAC5). Such a compound represents a valuable addition to a limited number of small-molecule probes to study the biological functions of individual endogenous mAC isoforms.
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
<a href="/en/project/LTAUSA18086" target="_blank" >LTAUSA18086: Design, synthesis and biological evaluation of potential modulators of human adenylate cyclases</a><br>
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
Bioorganic & Medicinal Chemistry
ISSN
0968-0896
e-ISSN
1464-3391
Volume of the periodical
95
Issue of the periodical within the volume
November
Country of publishing house
GB - UNITED KINGDOM
Number of pages
18
Pages from-to
117508
UT code for WoS article
001107116900001
EID of the result in the Scopus database
2-s2.0-85175552252