Planta Med 2008; 74(4): 438-444
DOI: 10.1055/s-2008-1034348
Natural Products Chemistry
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Girolline: A Potential Lead Structure For Antiplasmodial Drug Research

Françoise Benoit-Vical1 , 2 , 4 , Mariette Saléry2 , 4 , Patrice Njomnang Soh1 , 2 , Alain Ahond3 , Christiane Poupat3
  • 1Laboratoire de Chimie de Coordination du CNRS, UPR8241, Toulouse, France
  • 2Service de Parasitologie-Mycologie, Centre Hospitalier Universitaire de Rangueil, Toulouse, France
  • 3Institut de Chimie des Substances Naturelles du CNRS, Gif-sur-Yvette cedex, France
  • 4These co-authors (FBV and MS have contributed equally to this manuscript
Dedicated to Pierre Potier who initiated marine chemistry in the I.C.S.N. and was fully involved in the girolline project
Further Information

Publication History

Received: November 8, 2007 Revised: February 4, 2008

Accepted: February 6, 2008

Publication Date:
25 March 2008 (online)

Abstract

Girolline is a 2-aminoimidazole derivative extracted from Cymbastela cantharella (a New-Caledonian sponge) that has shown antitumor activity. In this study, we investigated its antimalarial activity and the point of action within the erythrocytic cycle of Plasmodium falciparum. Initially, we tested girolline and some synthetic analogues in vitro against four P. falciparum strains. The IC50 values of girolline ranged from 77 to 215 nM, and as with artemisinin or chloroquine, girolline inhibited parasitic growth by 100 %. Girolline was found to be active at a dose of 1 mg/kg/d (orally and intraperitoneally) in vivo. Moreover, there was a significant synergistic effect between girolline and chloroquine in vitro. The investigation of the mechanism of action of girolline during the erythrocytic life cycle of the parasite showed that its action targets the synthesis of proteins by the parasite. With such a biological profile, girolline could be considered as a model chemical structure for new candidates in the arsenal of new drugs and in particular of drugs able to fight malaria.

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Dr. F. Benoit-Vical

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