Title |
The effect of novel [3-fluoro-(2-phosphonoethoxy)propyl]purines on the inhibition of Plasmodium falciparum, Plasmodium vivax and human hypoxanthine–guanine–(xanthine) phosphoribosyltransferases
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Published in |
European Journal of Medicinal Chemistry, June 2013
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DOI | 10.1016/j.ejmech.2013.06.032 |
Pubmed ID | |
Authors |
Ondřej Baszczyňski, Dana Hocková, Zlatko Janeba, Antonín Holý, Petr Jansa, Martin Dračínský, Dianne T. Keough, Luke W. Guddat |
Abstract |
Protozoan parasites from the Plasmodiidae family are the causative agents of malaria. Inhibition of hypoxanthine-guanine-(xanthine) phosphoribosyltransferase (HG(X)PRT) has been suggested as a target for development of new anti-malarial therapeutics. Acyclic nucleoside phosphonates (ANPs) are potent and selective inhibitors of plasmodial HG(X)PRTs. A new series of ANPs, based on the chemical structure and inhibitory activity of three ANPs, 2-(phosphonoethoxy)ethyl with either guanine or hypoxanthine as the base (PEEG and PEEHx) and 3-hydroxy-2-(phosphonomethoxy)propyl with guanine as the base (HPMPG), were prepared. These compounds are stereoisomers of 3-fluoro-(2-phosphonoethoxy)propyl (FPEPs) and 3-fluoro-(2-phosphonomethoxy)propyl (FPMPs) analogues. Both the (R)- and (S)-isomers of these fluorinated derivatives have higher Ki values (by 10- to 1000-fold) for human HGPRT and Plasmodium falciparum HGXPRT than the non-fluorinated ANPs. Possible explanations for these changes in affinity are proposed based on docking studies using the known crystal structures of human HGPRT in complex with PEEG. |
X Demographics
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United Kingdom | 1 | 100% |
Demographic breakdown
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 19 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 5 | 26% |
Student > Ph. D. Student | 4 | 21% |
Student > Bachelor | 3 | 16% |
Researcher | 2 | 11% |
Unspecified | 1 | 5% |
Other | 3 | 16% |
Unknown | 1 | 5% |
Readers by discipline | Count | As % |
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Chemistry | 11 | 58% |
Biochemistry, Genetics and Molecular Biology | 3 | 16% |
Environmental Science | 2 | 11% |
Agricultural and Biological Sciences | 1 | 5% |
Unspecified | 1 | 5% |
Other | 0 | 0% |
Unknown | 1 | 5% |