5l42
From Proteopedia
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/PTR1_LEIMA PTR1_LEIMA]] Exhibits a NADPH-dependent biopterin reductase activity. Has good activity with folate and significant activity with dihydrofolate and dihydrobiopterin, but not with quinonoid dihydrobiopterin. Confers resistance to methotrexate (MTX).<ref>PMID:7972081</ref> | [[http://www.uniprot.org/uniprot/PTR1_LEIMA PTR1_LEIMA]] Exhibits a NADPH-dependent biopterin reductase activity. Has good activity with folate and significant activity with dihydrofolate and dihydrobiopterin, but not with quinonoid dihydrobiopterin. Confers resistance to methotrexate (MTX).<ref>PMID:7972081</ref> | ||
+ | <div style="background-color:#fffaf0;"> | ||
+ | == Publication Abstract from PubMed == | ||
+ | Flavonoids have previously been identified as antiparasitic agents and pteridine reductase 1 (PTR1) inhibitors. Herein, we focus our attention on the chroman-4-one scaffold. Three chroman-4-one analogues (1-3) of previously published chromen-4-one derivatives were synthesized and biologically evaluated against parasitic enzymes (Trypanosoma brucei PTR1-TbPTR1 and Leishmania major-LmPTR1) and parasites (Trypanosoma brucei and Leishmania infantum). A crystal structure of TbPTR1 in complex with compound 1 and the first crystal structures of LmPTR1-flavanone complexes (compounds 1 and 3) were solved. The inhibitory activity of the chroman-4-one and chromen-4-one derivatives was explained by comparison of observed and predicted binding modes of the compounds. Compound 1 showed activity both against the targeted enzymes and the parasites with a selectivity index greater than 7 and a low toxicity. Our results provide a basis for further scaffold optimization and structure-based drug design aimed at the identification of potent anti-trypanosomatidic compounds targeting multiple PTR1 variants. | ||
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+ | Chroman-4-One Derivatives Targeting Pteridine Reductase 1 and Showing Anti-Parasitic Activity.,Di Pisa F, Landi G, Dello Iacono L, Pozzi C, Borsari C, Ferrari S, Santucci M, Santarem N, Cordeiro-da-Silva A, Moraes CB, Alcantara LM, Fontana V, Freitas-Junior LH, Gul S, Kuzikov M, Behrens B, Pohner I, Wade RC, Costi MP, Mangani S Molecules. 2017 Mar 8;22(3). pii: E426. doi: 10.3390/molecules22030426. PMID:28282886<ref>PMID:28282886</ref> | ||
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+ | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
+ | </div> | ||
+ | <div class="pdbe-citations 5l42" style="background-color:#fffaf0;"></div> | ||
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+ | ==See Also== | ||
+ | *[[Pteridine reductase|Pteridine reductase]] | ||
== References == | == References == | ||
<references/> | <references/> |
Revision as of 10:01, 27 September 2017
Leishmania major Pteridine reductase 1 (PTR1) in complex with compound 3
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