Antimalarial activity of prodrugs of N-branched acyclic nucleoside phosphonate inhibitors of 6-oxopurine phosphoribosyltransferases

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F15%3A00448335" target="_blank" >RIV/61388963:_____/15:00448335 - isvavai.cz</a>
Result on the web
<a href="http://dx.doi.org/10.1016/j.bmc.2015.07.038" target="_blank" >http://dx.doi.org/10.1016/j.bmc.2015.07.038</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.bmc.2015.07.038" target="_blank" >10.1016/j.bmc.2015.07.038</a>

Result language
angličtina
Original language name
Antimalarial activity of prodrugs of N-branched acyclic nucleoside phosphonate inhibitors of 6-oxopurine phosphoribosyltransferases
Original language description
Acyclic nucleoside phosphonates (ANPs) that contain a 6-oxopurine base are good inhibitors of the human and Plasmodium falciparum 6-oxopurine phosphoribosyltransferases (PRTs), key enzymes of the purine salvage pathway. Chemical modifications, based on the crystal structures of several inhibitors in complex with the human PRTase, led to the design of a new class of inhibitors-the aza-ANPs. Because of the negative charges of the phosphonic acid moiety, their ability to cross cell membranes is, however, limited. Thus, phosphoramidate prodrugs of the aza-ANPs were prepared to improve permeability. These prodrugs arrest parasitemia with IC50 values in the micromolar range against Plasmodium falciparum-infected erythrocyte cultures (both chloroquine-sensitive and chloroquine-resistant Pf strains). The prodrugs exhibit low cytotoxicity in several human cell lines. Thus, they fulfill two essential criteria to qualify them as promising antimalarial drug leads.
Czech name
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Czech description
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Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CC - Organic chemistry
OECD FORD branch
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Project
<a href="/en/project/GAP207%2F11%2F0108" target="_blank" >GAP207/11/0108: Novel types of acyclic nucleoside phosphonates with potential antimalarial activity:hypoxanthine-guanine-xanthine phosphoribosyltransferase inhibitors</a><br>
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year
2015
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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