title: In vitro metabolism of grandisin, a lignan with anti-chagasic activity.
abstract: Tetrahydrofuran lignans represent a well-known group of phenolic compounds capable of acting as antiparasitic agents. In the search for new medicines for the treatment of Chagas disease, one promising compound is grandisin which has shown significant activity on trypomastigote forms of Trypanosoma cruzi. In this work, the in vitro metabolism of grandisin was studied in the pig cecum model and by biomimetic phase I reactions, aiming at an ensuing a preclinical pharmacokinetic investigation. Although grandisin exhibited no metabolization by the pig microbiota, one putative metabolite was formed in a biomimetic model using Jacobsen catalyst. The putative metabolite was tested against T. cruzi revealing loss of activity in comparison to grandisin.
authors.affiliation: Lychnoflora Pesquisa e Desenvolvimento em Produtos Naturais LTDA, Campus USP, Ribeirão Preto, SP, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: De Santis Ferreira
authors.forename: Daniel Roberto
authors.initials: DR
authors.lastname: Callejon
authors.forename: Anna
authors.initials: A
authors.lastname: Engemann
authors.forename: Benedikt
authors.initials: B
authors.lastname: Cramer
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Humpf
authors.forename: Valéria Priscila
authors.initials: VP
authors.lastname: de Barros
authors.forename: Marilda das Dores
authors.initials: Md
authors.lastname: Assis
authors.forename: Denise Brentan
authors.initials: DB
authors.lastname: da Silva
authors.forename: Sérgio
authors.initials: S
authors.lastname: de Albuquerque
authors.forename: Laura Tiemi
authors.initials: LT
authors.lastname: Okano
authors.forename: Massuo Jorge
authors.initials: MJ
authors.lastname: Kato
authors.forename: Norberto Peporine
authors.initials: NP
authors.lastname: Lopes
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D002432:Cecum / Q000469:parasitology; D014355:Chagas Disease / Q000188:drug therapy*; D005663:Furans / Q000378:metabolism* / Q000494:pharmacology*; D017705:Lignans / Q000378:metabolism* / Q000494:pharmacology*; D015394:Molecular Structure; D031701:Piper / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D013552:Swine; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D005663:Furans; D017705:Lignans; D010936:Plant Extracts; C074346:grandisin