FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2016703030> ?p ?o ?g. }

• W2016703030 endingPage "851" @default.
• W2016703030 startingPage "843" @default.
• W2016703030 abstract "Indoline derivatives possess therapeutic potential within a variety of drug candidates. In this study, we found that indoline is aromatized by cytochrome P450 (P450) enzymes to produce indole through a novel dehydrogenation pathway. The indole products can potentially be bioactivated to toxic intermediates through an additional dehydrogenation step. For example, 3-substituted indoles like 3-methylindole and zafirlukast [4-(5-cyclopentyloxy-carbonylamino-1-methyl-indol-3-ylmethyl)-3-methoxy-<i>N</i>-<i>o</i>-tolylsulfonylbenzamide] are dehydrogenated to form 3-methyleneindolenine electrophiles, which react with protein and/or DNA nucleophilic residues to cause toxicities. Another potentially significant therapeutic consequence of indoline aromatization is that the product indoles might have dramatically different therapeutic potency than the parent indolines. In this study, indoline was indeed efficiently aromatized by human liver microsomes and by several P450s, but not by flavin-containing monooxygenase (FMO) 3. CYP3A4 had the highest aromatase activity. Four additional indoline metabolites [2,3,4,7-tetrahydro-4,5-epoxy-1<i>H</i>-indole (M1); <i>N-</i>hydroxyindole (M2), <i>N-</i>hydroxyindoline (M3), and M4 ([1,4,2,5]dioxadiazino[2,3-<i>a</i>:5,6-<i>a</i>′]diindole)] were characterized; none was a metabolite of indole. M1 was an arene oxide from P450 oxidation, and M2, M3, and M4 were produced by FMO3. Our data indicated that indoline was oxidized to M3 and then to an intermediate indoline nitrone, which tautomerized to form M2, and subsequently dimerized to a di-indoline. This dimer was immediately oxidized by FMO3 or atmospheric oxygen to the final product, M4. No evidence was found for the P450-mediated production of an aliphatic alcohol from indoline that might dehydrate to produce indole. Therefore, P450 enzymes catalyze the novel “aromatase” metabolism of indoline to produce indole. The aromatase mechanism does not seem to occur through <i>N-</i>oxidation or dehydration of an alcohol but rather through a formal dehydrogenation pathway." @default.
• W2016703030 created "2016-06-24" @default.
• W2016703030 creator A5001492458 @default.
• W2016703030 creator A5012620497 @default.
• W2016703030 creator A5022840154 @default.
• W2016703030 creator A5066694016 @default.
• W2016703030 creator A5081011722 @default.
• W2016703030 creator A5086365093 @default.
• W2016703030 date "2007-05-14" @default.
• W2016703030 modified "2023-09-30" @default.
• W2016703030 title "Dehydrogenation of Indoline by Cytochrome P450 Enzymes: A Novel “Aromatase” Process" @default.
• W2016703030 cites W1487547957 @default.
• W2016703030 cites W1562164760 @default.
• W2016703030 cites W1972047614 @default.
• W2016703030 cites W1986333080 @default.
• W2016703030 cites W1987212108 @default.
• W2016703030 cites W1988356342 @default.
• W2016703030 cites W1995599900 @default.
• W2016703030 cites W2017007352 @default.
• W2016703030 cites W2022792542 @default.
• W2016703030 cites W2022949318 @default.
• W2016703030 cites W2025152270 @default.
• W2016703030 cites W2032071351 @default.
• W2016703030 cites W2067559257 @default.
• W2016703030 cites W2071288068 @default.
• W2016703030 cites W2072121992 @default.
• W2016703030 cites W2075212824 @default.
• W2016703030 cites W2075249384 @default.
• W2016703030 cites W2091958115 @default.
• W2016703030 cites W2107425171 @default.
• W2016703030 cites W2112380126 @default.
• W2016703030 cites W2148419752 @default.
• W2016703030 cites W2165956237 @default.
• W2016703030 cites W2172334773 @default.
• W2016703030 cites W2912608550 @default.
• W2016703030 cites W3023537059 @default.
• W2016703030 cites W4237567490 @default.
• W2016703030 doi "https://doi.org/10.1124/jpet.107.121723" @default.
• W2016703030 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17502430" @default.
• W2016703030 hasPublicationYear "2007" @default.
• W2016703030 type Work @default.
• W2016703030 sameAs 2016703030 @default.
• W2016703030 citedByCount "32" @default.
• W2016703030 countsByYear W20167030302012 @default.
• W2016703030 countsByYear W20167030302013 @default.
• W2016703030 countsByYear W20167030302014 @default.
• W2016703030 countsByYear W20167030302015 @default.
• W2016703030 countsByYear W20167030302016 @default.
• W2016703030 countsByYear W20167030302017 @default.
• W2016703030 countsByYear W20167030302018 @default.
• W2016703030 countsByYear W20167030302019 @default.
• W2016703030 countsByYear W20167030302020 @default.
• W2016703030 countsByYear W20167030302021 @default.
• W2016703030 countsByYear W20167030302022 @default.
• W2016703030 countsByYear W20167030302023 @default.
• W2016703030 crossrefType "journal-article" @default.
• W2016703030 hasAuthorship W2016703030A5001492458 @default.
• W2016703030 hasAuthorship W2016703030A5012620497 @default.
• W2016703030 hasAuthorship W2016703030A5022840154 @default.
• W2016703030 hasAuthorship W2016703030A5066694016 @default.
• W2016703030 hasAuthorship W2016703030A5081011722 @default.
• W2016703030 hasAuthorship W2016703030A5086365093 @default.
• W2016703030 hasConcept C119889771 @default.
• W2016703030 hasConcept C13002179 @default.
• W2016703030 hasConcept C161790260 @default.
• W2016703030 hasConcept C181199279 @default.
• W2016703030 hasConcept C185592680 @default.
• W2016703030 hasConcept C192527728 @default.
• W2016703030 hasConcept C2779325354 @default.
• W2016703030 hasConcept C2779890007 @default.
• W2016703030 hasConcept C526171541 @default.
• W2016703030 hasConcept C55493867 @default.
• W2016703030 hasConcept C71240020 @default.
• W2016703030 hasConceptScore W2016703030C119889771 @default.
• W2016703030 hasConceptScore W2016703030C13002179 @default.
• W2016703030 hasConceptScore W2016703030C161790260 @default.
• W2016703030 hasConceptScore W2016703030C181199279 @default.
• W2016703030 hasConceptScore W2016703030C185592680 @default.
• W2016703030 hasConceptScore W2016703030C192527728 @default.
• W2016703030 hasConceptScore W2016703030C2779325354 @default.
• W2016703030 hasConceptScore W2016703030C2779890007 @default.
• W2016703030 hasConceptScore W2016703030C526171541 @default.
• W2016703030 hasConceptScore W2016703030C55493867 @default.
• W2016703030 hasConceptScore W2016703030C71240020 @default.
• W2016703030 hasIssue "2" @default.
• W2016703030 hasLocation W20167030301 @default.
• W2016703030 hasLocation W20167030302 @default.
• W2016703030 hasOpenAccess W2016703030 @default.
• W2016703030 hasPrimaryLocation W20167030301 @default.
• W2016703030 hasRelatedWork W1662206987 @default.
• W2016703030 hasRelatedWork W2003504283 @default.
• W2016703030 hasRelatedWork W2009067244 @default.
• W2016703030 hasRelatedWork W2015738027 @default.
• W2016703030 hasRelatedWork W2020041384 @default.
• W2016703030 hasRelatedWork W2137896734 @default.
• W2016703030 hasRelatedWork W2498151553 @default.
• W2016703030 hasRelatedWork W2949314698 @default.
• W2016703030 hasRelatedWork W3084121513 @default.

• next