Synthesis and evaluation of symmetric acyclic nucleoside bisphosphonates as inhibitors of the Plasmodium falciparum, Plasmodium vivax and human 6-oxopurine phosphoribosyltransferases and the antimalarial activity of their prodrugs
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00477558" target="_blank" >RIV/61388963:_____/17:00477558 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1016/j.bmc.2017.05.048" target="_blank" >http://dx.doi.org/10.1016/j.bmc.2017.05.048</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bmc.2017.05.048" target="_blank" >10.1016/j.bmc.2017.05.048</a>
Alternative languages
Result language
angličtina
Original language name
Synthesis and evaluation of symmetric acyclic nucleoside bisphosphonates as inhibitors of the Plasmodium falciparum, Plasmodium vivax and human 6-oxopurine phosphoribosyltransferases and the antimalarial activity of their prodrugs
Original language description
Two new series of symmetric acyclic nucleoside bisphosphonates (ANbPs) have been synthesised as potential inhibitors of the Plasmodium falciparum (Pf) and vivax (Pv) 6-oxopurine phosphoribosyltransferases. The structural variability between these symmetric ANbPs lies in the number of atoms in the two acyclic linkers connecting the N-9 atom of the purine base to each of two phosphonate groups and the branching point of the acyclic moiety relative to the purine base, which occurs at either the alpha or beta positions. Within each series, six different 6-oxopurine bases have been attached. In general, the ANbPs with either guanine or hypoxanthine have lower K-i values than for those containing either the 8-bromo or 7-deaza 6-oxopurine bases. The lowest K-i values obtained for the two parasite enzymes were 0.1 mu M (Pf) and 0.2 mu M (Pv) for this series of compounds. Two phosphoramidate prodrugs of these inhibitors exhibited antimalarial activity against Pf in infected erythrocyte cell culture with IC50 values of 0.8 and 1.5 mu M. These two compounds exhibited low cytotoxicity in human A549 cells having CC50 values of >300 mu M resulting in an excellent selectivity index.
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
Bioorganic & Medicinal Chemistry
ISSN
0968-0896
e-ISSN
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Volume of the periodical
25
Issue of the periodical within the volume
15
Country of publishing house
GB - UNITED KINGDOM
Number of pages
23
Pages from-to
4008-4030
UT code for WoS article
000406022200011
EID of the result in the Scopus database
2-s2.0-85020383102