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• W2214474074 endingPage "125" @default.
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• W2214474074 abstract "ABSTRACT The heme-containing enzymes indoleamine 2,3-dioxygenase-1 (IDO-1) and IDO-2 catalyze the conversion of the essential amino acid tryptophan into kynurenine. Metabolites of the kynurenine pathway and IDO itself are involved in immunity and the pathology of several diseases, having either immunoregulatory or antimicrobial effects. IDO-1 plays a central role in the pathogenesis of cerebral malaria, which is the most severe and often fatal neurological complication of infection with Plasmodium falciparum . Mouse models are usually used to study the underlying pathophysiology. In this study, we screened a natural compound library against mouse IDO-1 and identified 8-aminobenzo[ b ]quinolizinium (compound 2c) to be an inhibitor of IDO-1 with potency at nanomolar concentrations (50% inhibitory concentration, 164 nM). Twenty-one structurally modified derivatives of compound 2c were synthesized for structure-activity relationship analyses. The compounds were found to be selective for IDO-1 over IDO-2. We therefore compared the roles of prominent amino acids in the catalytic mechanisms of the two isoenzymes via homology modeling, site-directed mutagenesis, and kinetic analyses. Notably, methionine 385 of IDO-2 was identified to interfere with the entrance of l -tryptophan to the active site of the enzyme, which explains the selectivity of the inhibitors. Most interestingly, several benzo[ b ]quinolizinium derivatives (6 compounds with 50% effective concentration values between 2.1 and 6.7 nM) were found to be highly effective against P. falciparum 3D7 blood stages in cell culture with a mechanism independent of IDO-1 inhibition. We believe that the class of compounds presented here has unique characteristics; it combines the inhibition of mammalian IDO-1 with strong antiparasitic activity, two features that offer potential for drug development." @default.
• W2214474074 created "2016-06-24" @default.
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• W2214474074 date "2016-01-01" @default.
• W2214474074 modified "2023-10-15" @default.
• W2214474074 title "Benzo[ <i>b</i> ]quinolizinium Derivatives Have a Strong Antimalarial Activity and Inhibit Indoleamine Dioxygenase" @default.
• W2214474074 cites W115657779 @default.
• W2214474074 cites W1231151993 @default.
• W2214474074 cites W1520396038 @default.
• W2214474074 cites W1956013940 @default.
• W2214474074 cites W1965240438 @default.
• W2214474074 cites W1969503178 @default.
• W2214474074 cites W1975929837 @default.
• W2214474074 cites W1978152393 @default.
• W2214474074 cites W1979648475 @default.
• W2214474074 cites W1980907312 @default.
• W2214474074 cites W1984811585 @default.
• W2214474074 cites W1987061320 @default.
• W2214474074 cites W1989457118 @default.
• W2214474074 cites W1994981478 @default.
• W2214474074 cites W1996005089 @default.
• W2214474074 cites W2000697519 @default.
• W2214474074 cites W2003356525 @default.
• W2214474074 cites W2003589493 @default.
• W2214474074 cites W2008249034 @default.
• W2214474074 cites W2008878335 @default.
• W2214474074 cites W2012906058 @default.
• W2214474074 cites W2020251171 @default.
• W2214474074 cites W2021386451 @default.
• W2214474074 cites W2022548526 @default.
• W2214474074 cites W2025969665 @default.
• W2214474074 cites W2031194866 @default.
• W2214474074 cites W2034521426 @default.
• W2214474074 cites W2038938429 @default.
• W2214474074 cites W2040829106 @default.
• W2214474074 cites W2043390055 @default.
• W2214474074 cites W2046199004 @default.
• W2214474074 cites W2050488993 @default.
• W2214474074 cites W2053217888 @default.
• W2214474074 cites W2059246725 @default.
• W2214474074 cites W2069731779 @default.
• W2214474074 cites W2070110861 @default.
• W2214474074 cites W2070365236 @default.
• W2214474074 cites W2076127956 @default.
• W2214474074 cites W2080503518 @default.
• W2214474074 cites W2080892289 @default.
• W2214474074 cites W2081167662 @default.
• W2214474074 cites W2081538358 @default.
• W2214474074 cites W2081759687 @default.
• W2214474074 cites W2093792921 @default.
• W2214474074 cites W2105668259 @default.
• W2214474074 cites W2110888323 @default.
• W2214474074 cites W2111537995 @default.
• W2214474074 cites W2114918609 @default.
• W2214474074 cites W2117000356 @default.
• W2214474074 cites W2118052242 @default.
• W2214474074 cites W2121681183 @default.
• W2214474074 cites W2128146197 @default.
• W2214474074 cites W2128635872 @default.
• W2214474074 cites W2132764522 @default.
• W2214474074 cites W2135627297 @default.
• W2214474074 cites W2138645583 @default.
• W2214474074 cites W2138900524 @default.
• W2214474074 cites W2147547451 @default.
• W2214474074 cites W2152301430 @default.
• W2214474074 cites W2152524078 @default.
• W2214474074 cites W2152791364 @default.
• W2214474074 cites W2159255337 @default.
• W2214474074 cites W2164554578 @default.
• W2214474074 cites W2164739251 @default.
• W2214474074 cites W2165777029 @default.
• W2214474074 cites W2166508115 @default.
• W2214474074 cites W2169259021 @default.
• W2214474074 cites W2169931678 @default.
• W2214474074 cites W2176280103 @default.
• W2214474074 cites W2321721989 @default.
• W2214474074 cites W2324723757 @default.
• W2214474074 cites W2335692183 @default.
• W2214474074 cites W2949752691 @default.
• W2214474074 cites W2953202336 @default.
• W2214474074 cites W4293247451 @default.
• W2214474074 cites W2091527431 @default.
• W2214474074 doi "https://doi.org/10.1128/aac.01066-15" @default.
• W2214474074 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4704160" @default.
• W2214474074 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26459907" @default.
• W2214474074 hasPublicationYear "2016" @default.
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