Acyclic Nucleoside Phosphonates Containing 9-Deazahypoxanthine and a Five-Membered Heterocycle as Selective Inhibitors of Plasmodial 6-Oxopurine Phosphoribosyltransferases
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00478407" target="_blank" >RIV/61388963:_____/17:00478407 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1002/cmdc.201700293" target="_blank" >http://dx.doi.org/10.1002/cmdc.201700293</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1002/cmdc.201700293" target="_blank" >10.1002/cmdc.201700293</a>
Alternative languages
Result language
angličtina
Original language name
Acyclic Nucleoside Phosphonates Containing 9-Deazahypoxanthine and a Five-Membered Heterocycle as Selective Inhibitors of Plasmodial 6-Oxopurine Phosphoribosyltransferases
Original language description
Acyclic nucleoside phosphonates (ANPs) are an important class of therapeutic drugs that act as antiviral agents by inhibiting viral DNA polymerases and reverse transcriptases. ANPs containing a 6-oxopurine unit instead of a 6-aminopurine or pyrimidine base are inhibitors of the purine salvage enzyme, hypoxanthine-guanine-[xanthine] phosphoribosyltransferase (HG[X]PRT). Such compounds, and their prodrugs, are able to arrest the growth of Plasmodium falciparum (Pf) in cell culture. A new series of ANPs were synthesized and tested as inhibitors of human HGPRT, PfHGXPRT, and Plasmodium vivax (Pv) HGPRT. The novelty of these compounds is that they contain a five-membered heterocycle (imidazoline, imidazole, or triazole) inserted between the acyclic linker(s) and the nucleobase, namely, 9-deazahypoxanthine. Five of the compounds were found to be micromolar inhibitors of PfHGXPRT and PvHGPRT, but no inhibition of human HGPRT was observed under the same assay conditions. This demonstrates selectivity of these types of compounds for the two parasitic enzymes compared to the human counterpart and confirms the importance of the chemical nature of the acyclic moiety in conferring affinity/selectivity for these three enzymes.
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/GA16-06049S" target="_blank" >GA16-06049S: Inhibitors of 6-oxopurine phosphoribosyltransferases based on acyclic nucleoside phosphonates: Potential novel antibacterial and antiparasitic agents</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2017
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
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Volume of the periodical
12
Issue of the periodical within the volume
14
Country of publishing house
DE - GERMANY
Number of pages
9
Pages from-to
1133-1141
UT code for WoS article
000407432900005
EID of the result in the Scopus database
2-s2.0-85022332657