HPLC and HPLC-MS analysis of intestinal elimination and phase 2 metabolism of 4'-hydroxy-4-methoxychalcone and its bis-Mannich analog in the rat

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dc.creatorValeze, Aline Bernardes
dc.creatorKuzma, Mónika
dc.creatorAlmási, Attila
dc.creatorNoda Pérez, Caridad
dc.creatorPerjési, Pál
dc.date.accessioned2023-08-25T15:35:18Z
dc.date.available2023-08-25T15:35:18Z
dc.date.issued2022
dc.description.abstractAims: The aim was to study the elimination and Phase 2 biotransformation of 4'-hydroxy-4-methoxychalcone (1) and its bis-Mannich analog (2) in the small intestine of the rat. Background: Earlier studies indicated that chalcones are promising starting points for drug design. Aminomethylation of drugs is considered to improve their delivery into the human body. Objectives: To set up validated HPLC-UV methods to quantitate the investigated chalcones in the rat intestinal perfusates. Comparison of intestinal disappearance and Phase 2 metabolic profile of the 4’-hydroxychalcone (1) and a bis-Mannich analog (2). Methods: Chalcones 1 and 2 were luminally perfused in the small intestine of rats at a concentration of 240 μM and 280 μM, respectively. Analysis of the collected intestinal perfusate samples was performed by a validated HPLC-UV method. Using HPLC-MS, the samples were analyzed for Phase 2 metabolites as well. Results: Elimination kinetics of the two 4’-hydroxychalcones displayed characteristic differences having the nonpolar chalcone 1 higher elimination rate over the 90-minute ex vivo experiments. HPLC-MS analysis of the perfusates indicated the presence of glucuronide, sulfate, and glutathione conjugates in the parent molecules. Intestinal disappearance and sulfation of the bis-Mannich derivative 2 showed characteristic differences compared to 1 Conclusion: The results demonstrate, to the best of our knowledge, for the first time, how the title structural modification of phenolic chalcones affects intestinal elimination and Phase 2 metabolism of the compounds Highlights: Study on ex vivo intestinal elimination of a 4'-hydroxy-4-methoxychalcone and its bis-Mannich analog. Development of validated HPLC-UV methods for quantitation of 4’-hydroxychalcone derivatives in rat intestinal perfusates. HPLC-MS identification of Phase 2 metabolites of 4’-hydroxychalcones in rat intestinal perfusates.pt_BR
dc.identifier.citationBERNARDES, Aline et al. HPLC and HPLC-MS analysis of intestinal elimination and phase 2 metabolism of 4'-hydroxy-4-methoxychalcone and its bis-Mannich analog in the rat. The Open Medicinal Chemistry Journal, [s. l.], v. 16, e187410452208110, 2022. DOI: 10.2174/18741045-v16-e2208110. Disponível em: https://openmedicinalchemistryjournal.com/VOLUME/16/ELOCATOR/e187410452208110/. Acesso em: 24 ago. 2023.pt_BR
dc.identifier.doi10.2174/18741045-v16-e2208110
dc.identifier.issne- 1874-1045
dc.identifier.urihttp://repositorio.bc.ufg.br/handle/ri/23437
dc.language.isoengpt_BR
dc.publisher.countryHolandapt_BR
dc.publisher.departmentInstituto de Química - IQ (RMG)pt_BR
dc.rightsAcesso Abertopt_BR
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectHydroxychalconespt_BR
dc.subjectMannich basespt_BR
dc.subjectHPLC, HPLC-MSpt_BR
dc.subjectIntestinal absorptionpt_BR
dc.subjectIntestinal metabolismpt_BR
dc.titleHPLC and HPLC-MS analysis of intestinal elimination and phase 2 metabolism of 4'-hydroxy-4-methoxychalcone and its bis-Mannich analog in the ratpt_BR
dc.typeArtigopt_BR

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