FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1968331348> ?p ?o ?g. }

• W1968331348 endingPage "62" @default.
• W1968331348 startingPage "53" @default.
• W1968331348 abstract "Although tamoxifen is approved for the treatment of hormone-dependent breast cancer as well as for the prevention of breast cancer in high-risk women, several studies in animal models have shown that tamoxifen is heptocarcinogenic, and in humans, tamoxifen has been associated with an increased risk of endometrial cancer. One potential mechanism of tamoxifen carcinogenesis could involve metabolism of tamoxifen to 3,4-dihydroxytamoxifen followed by oxidation to a highly reactive o-quinone which has the potential to alkylate and/or oxidize cellular macromolecules in vivo. In the study presented here, we synthesized the 3,4-dihydroxytamoxifen, prepared its o-quinone chemically and enzymatically, and studied the reactivity of the o-quinone with GSH and deoxynucleosides. The E (trans) and Z (cis) isomers of 3,4-dihydroxytamoxifen were synthesized using a concise synthetic pathway (four steps). This approach is based on the McMurry reaction between the key 4-(2-chloroethoxy)-3,4-methylenedioxybenzophenone and propiophenone, followed by selective removal of the methylenedioxy ring of (E, Z)-1-[4-[2-(N,N-dimethylamino)ethoxy]phenyl]-1-(3, 4-methylenedioxyphenyl)-2-phenyl-1-butene with BCl(3). Oxidation of 3,4-dihydroxytamoxifen by activated silver oxide or tyrosinase gave 3,4-dihydroxytamoxifen-o-quinone as a mixture of E and Z isomers. The resulting o-quinone has a half-life of approximately 80 min under physiological conditions. Reaction of the o-quinone with GSH gave two di-GSH conjugates and three mono GSH conjugates. Incubation of 3,4-dihydroxytamoxifen with GSH in the presence of microsomal P450 gave the same GSH conjugates which were also detected in incubations with human breast cancer cells (MCF-7). Reaction of 3, 4-dihydroxytamoxifen-o-quinone with deoxynucleosides gave only thymidine and deoxyguanosine adducts; neither deoxyadenosine nor deoxycytosine adducts were detected. Preliminary studies conducted with human breast cancer cell lines showed that 3, 4-dihydroxytamoxifen exhibited cytotoxic potency similar to that of 4-hydroxytamoxifen and tamoxifen in an estrogen receptor negative (ER(-)) cell line (MDA-MB-231); however, in the ER(+) cell line (MCF-7), the catechol metabolite was about half as toxic as the other two compounds. Finally, in the presence of microsomes and GSH, 4-hydroxytamoxifen gave predominantly quinone methide GSH conjugates as reported in the previous paper in this issue [Fan, P. W., et al. (2000) Chem. Res. Toxicol. 13, XX-XX]. However, in the presence of tyrosinase and GSH, 4-hydroxytamoxifen was primarily converted to o-quinone GSH conjugates. These results suggest that the catechol metabolite of tamoxifen has the potential to cause cytotoxicity in vivo through formation of 3,4-dihydroxytamoxifen-o-quinone." @default.
• W1968331348 created "2016-06-24" @default.
• W1968331348 creator A5001452107 @default.
• W1968331348 creator A5024769249 @default.
• W1968331348 creator A5026872517 @default.
• W1968331348 creator A5063701397 @default.
• W1968331348 creator A5087734530 @default.
• W1968331348 creator A5088160011 @default.
• W1968331348 date "1999-12-21" @default.
• W1968331348 modified "2023-10-07" @default.
• W1968331348 title "Synthesis and Reactivity of a Potential Carcinogenic Metabolite of Tamoxifen: 3,4-Dihydroxytamoxifen-<i>o</i>-quinone" @default.
• W1968331348 cites W1538841780 @default.
• W1968331348 cites W1978991747 @default.
• W1968331348 cites W1980882217 @default.
• W1968331348 cites W2020997123 @default.
• W1968331348 cites W2025911184 @default.
• W1968331348 cites W2028002837 @default.
• W1968331348 cites W2053261189 @default.
• W1968331348 cites W2060353880 @default.
• W1968331348 cites W2080931196 @default.
• W1968331348 cites W2085784829 @default.
• W1968331348 cites W2091327765 @default.
• W1968331348 cites W2235540603 @default.
• W1968331348 cites W2315154259 @default.
• W1968331348 cites W2331586116 @default.
• W1968331348 cites W2405564100 @default.
• W1968331348 doi "https://doi.org/10.1021/tx990145n" @default.
• W1968331348 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10649967" @default.
• W1968331348 hasPublicationYear "1999" @default.
• W1968331348 type Work @default.
• W1968331348 sameAs 1968331348 @default.
• W1968331348 citedByCount "73" @default.
• W1968331348 countsByYear W19683313482012 @default.
• W1968331348 countsByYear W19683313482013 @default.
• W1968331348 countsByYear W19683313482014 @default.
• W1968331348 countsByYear W19683313482015 @default.
• W1968331348 countsByYear W19683313482016 @default.
• W1968331348 countsByYear W19683313482018 @default.
• W1968331348 countsByYear W19683313482019 @default.
• W1968331348 countsByYear W19683313482021 @default.
• W1968331348 crossrefType "journal-article" @default.
• W1968331348 hasAuthorship W1968331348A5001452107 @default.
• W1968331348 hasAuthorship W1968331348A5024769249 @default.
• W1968331348 hasAuthorship W1968331348A5026872517 @default.
• W1968331348 hasAuthorship W1968331348A5063701397 @default.
• W1968331348 hasAuthorship W1968331348A5087734530 @default.
• W1968331348 hasAuthorship W1968331348A5088160011 @default.
• W1968331348 hasConcept C114246631 @default.
• W1968331348 hasConcept C121608353 @default.
• W1968331348 hasConcept C126322002 @default.
• W1968331348 hasConcept C142724271 @default.
• W1968331348 hasConcept C181199279 @default.
• W1968331348 hasConcept C185592680 @default.
• W1968331348 hasConcept C204787440 @default.
• W1968331348 hasConcept C2776910235 @default.
• W1968331348 hasConcept C2777176818 @default.
• W1968331348 hasConcept C2777477808 @default.
• W1968331348 hasConcept C2777550763 @default.
• W1968331348 hasConcept C2778407918 @default.
• W1968331348 hasConcept C2780643102 @default.
• W1968331348 hasConcept C530470458 @default.
• W1968331348 hasConcept C538909803 @default.
• W1968331348 hasConcept C55493867 @default.
• W1968331348 hasConcept C71240020 @default.
• W1968331348 hasConcept C71924100 @default.
• W1968331348 hasConceptScore W1968331348C114246631 @default.
• W1968331348 hasConceptScore W1968331348C121608353 @default.
• W1968331348 hasConceptScore W1968331348C126322002 @default.
• W1968331348 hasConceptScore W1968331348C142724271 @default.
• W1968331348 hasConceptScore W1968331348C181199279 @default.
• W1968331348 hasConceptScore W1968331348C185592680 @default.
• W1968331348 hasConceptScore W1968331348C204787440 @default.
• W1968331348 hasConceptScore W1968331348C2776910235 @default.
• W1968331348 hasConceptScore W1968331348C2777176818 @default.
• W1968331348 hasConceptScore W1968331348C2777477808 @default.
• W1968331348 hasConceptScore W1968331348C2777550763 @default.
• W1968331348 hasConceptScore W1968331348C2778407918 @default.
• W1968331348 hasConceptScore W1968331348C2780643102 @default.
• W1968331348 hasConceptScore W1968331348C530470458 @default.
• W1968331348 hasConceptScore W1968331348C538909803 @default.
• W1968331348 hasConceptScore W1968331348C55493867 @default.
• W1968331348 hasConceptScore W1968331348C71240020 @default.
• W1968331348 hasConceptScore W1968331348C71924100 @default.
• W1968331348 hasIssue "1" @default.
• W1968331348 hasLocation W19683313481 @default.
• W1968331348 hasLocation W19683313482 @default.
• W1968331348 hasOpenAccess W1968331348 @default.
• W1968331348 hasPrimaryLocation W19683313481 @default.
• W1968331348 hasRelatedWork W1967860679 @default.
• W1968331348 hasRelatedWork W1989855119 @default.
• W1968331348 hasRelatedWork W1996031616 @default.
• W1968331348 hasRelatedWork W2003302531 @default.
• W1968331348 hasRelatedWork W2029420773 @default.
• W1968331348 hasRelatedWork W2067042484 @default.
• W1968331348 hasRelatedWork W2072240003 @default.
• W1968331348 hasRelatedWork W2601211377 @default.
• W1968331348 hasRelatedWork W2950605813 @default.
• W1968331348 hasRelatedWork W2952515906 @default.

• next