Počet záznamů: 1
Acyclic Nucleoside Phosphonates Containing 9-Deazahypoxanthine and a Five-Membered Heterocycle as Selective Inhibitors of Plasmodial 6-Oxopurine Phosphoribosyltransferases
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SYSNO ASEP 0478407 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Acyclic Nucleoside Phosphonates Containing 9-Deazahypoxanthine and a Five-Membered Heterocycle as Selective Inhibitors of Plasmodial 6-Oxopurine Phosphoribosyltransferases Tvůrce(i) Kaiser, Martin Maxmilian (UOCHB-X) RID, ORCID
Baszczyňski, Ondřej (UOCHB-X) RID, ORCID
Hocková, Dana (UOCHB-X) RID, ORCID
Poštová Slavětínská, Lenka (UOCHB-X) RID
Dračínský, Martin (UOCHB-X) RID, ORCID
Keough, D. T. (AU)
Guddat, L. W. (AU)
Janeba, Zlatko (UOCHB-X) RID, ORCIDZdroj.dok. ChemMedChem. - : Wiley - ISSN 1860-7179
Roč. 12, č. 14 (2017), s. 1133-1141Poč.str. 9 s. Jazyk dok. eng - angličtina Země vyd. DE - Německo Klíč. slova inhibitors ; nucleosides ; malaria ; phosphonates ; purine salvage Vědní obor RIV CC - Organická chemie Obor OECD Organic chemistry CEP GA16-06049S GA ČR - Grantová agentura ČR Institucionální podpora UOCHB-X - RVO:61388963 UT WOS 000407432900005 EID SCOPUS 85022332657 DOI 10.1002/cmdc.201700293 Anotace 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. Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Rok sběru 2018
Počet záznamů: 1