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: 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
• Journal: Planta medica (Planta Med) Vol. 78 Issue 18 Pg. 1939-41 (Dec 2012) ISSN: 1439-0221 [Electronic] Germany
• PMID: 23150073 (Publication Type: Letter, Research Support, Non-U.S. Gov't)
• Copyright: Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• Antiprotozoal Agents
• Furans
• Lignans
• Plant Extracts
• grandisin

Topics

• Animals
• Antiprotozoal Agents (chemistry, pharmacokinetics)
• Cecum (parasitology)
• Chagas Disease (drug therapy)
• Furans (metabolism, pharmacology)
• Lignans (metabolism, pharmacology)
• Molecular Structure
• Piper (chemistry)
• Plant Extracts (chemistry, pharmacology)
• Swine
• Trypanosoma cruzi (drug effects)