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

Leandro De Santis Ferreira; Daniel Roberto Callejon; Anna Engemann; Benedikt Cramer; Hans-Ulrich Humpf; Valéria Priscila de Barros; Marilda das Dores Assis; Denise Brentan da Silva; Sérgio de Albuquerque; Laura Tiemi Okano; Massuo Jorge Kato; Norberto Peporine Lopes

doi:10.1055/s-0032-1327876

Planta Medica, Inhaltsverzeichnis

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

¹Lychnoflora Pesquisa e Desenvolvimento em Produtos Naturais LTDA, Campus USP, Ribeirão Preto, SP, Brazil

²Núcleo 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

¹Lychnoflora Pesquisa e Desenvolvimento em Produtos Naturais LTDA, Campus USP, Ribeirão Preto, SP, Brazil

,

Anna Engemann

³Institut für Lebensmittelchemie, Westfälische Wilhelms-Universität Münster, Münster, Germany

,

Benedikt Cramer

³Institut für Lebensmittelchemie, Westfälische Wilhelms-Universität Münster, Münster, Germany

,

Hans-Ulrich Humpf

³Institut für Lebensmittelchemie, Westfälische Wilhelms-Universität Münster, Münster, Germany

,

Valéria Priscila de Barros

²Núcleo 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

⁴Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Ribeirão Preto, SP, Brazil

,

Denise Brentan da Silva

¹Lychnoflora Pesquisa e Desenvolvimento em Produtos Naturais LTDA, Campus USP, Ribeirão Preto, SP, Brazil

,

Sérgio de Albuquerque

²Núcleo 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

⁴Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Ribeirão Preto, SP, Brazil

,

Massuo Jorge Kato

⁵Instituto de Química-Universidade de São Paulo (USP), São Paulo, SP, Brazil

,

Norberto Peporine Lopes

²Núcleo 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

› Institutsangaben

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

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Referenzen

References
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