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Planta Med 2012; 78(18): 1939-1941
DOI: 10.1055/s-0032-1327876
Pharmacokinetic Investigations
Letters
Georg Thieme Verlag KG Stuttgart · New York

In vitro Metabolism of Grandisin, a Lignan with Anti-chagasic Activity

Leandro De Santis Ferreira
1   Lychnoflora Pesquisa e Desenvolvimento em Produtos Naturais LTDA, Campus USP, Ribeirão Preto, SP, Brazil
2   Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP), Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil
,
Daniel Roberto Callejon
1   Lychnoflora Pesquisa e Desenvolvimento em Produtos Naturais LTDA, Campus USP, Ribeirão Preto, SP, Brazil
,
Anna Engemann
3   Institut für Lebensmittelchemie, Westfälische Wilhelms-Universität Münster, Münster, Germany
,
Benedikt Cramer
3   Institut für Lebensmittelchemie, Westfälische Wilhelms-Universität Münster, Münster, Germany
,
Hans-Ulrich Humpf
3   Institut für Lebensmittelchemie, Westfälische Wilhelms-Universität Münster, Münster, Germany
,
Valéria Priscila de Barros
2   Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP), Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil
,
Marilda das Dores Assis
4   Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Ribeirão Preto, SP, Brazil
,
Denise Brentan da Silva
1   Lychnoflora Pesquisa e Desenvolvimento em Produtos Naturais LTDA, Campus USP, Ribeirão Preto, SP, Brazil
,
Sérgio de Albuquerque
2   Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP), Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil
,
Laura Tiemi Okano
4   Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Ribeirão Preto, SP, Brazil
,
Massuo Jorge Kato
5   Instituto de Química-Universidade de São Paulo (USP), São Paulo, SP, Brazil
,
Norberto Peporine Lopes
2   Núcleo de Pesquisa em Produtos Naturais e Sintéticos (NPPNS), Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP), Universidade de São Paulo (USP), Ribeirão Preto, SP, Brazil
› Author Affiliations
Further Information

Publication History

received 29 June 2012
revised 27 September 2012

accepted 01 October 2012

Publication Date:
13 November 2012 (online)

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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.

Key words

tetrahydrofuran lignans - grandisin - in vitro metabolism - Piper solmsianum - Piperaceae - Jacobsen catalyst

Supporting Information

 

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