. A ' 4 -:, PHYTOTHERAPY RESEARCH, VOL. 11, 193-197 (1997) &.Y( Leishmanicidal and Trypanocidal Activity of Extracts and Secondary Metabolites from- " * Basidiomycetes Alba Inchausti', Gloria Yaluff', Antonieta Rojas de Arias'*, Susana Torres', Maria Elena Ferreira', Hector Nakayama', Alicia Schinini', Kirsten Lorenzen', Timm Anke' and Alain Fournet3 'Department of Tropical Medicine, IICS (Instituto de Investigaciones en Ciencias de la Salud), Rio de la Plata y Lagerenza, Casilla $ Correo 2511, Asuncion, Paraguay -LB Biotechnologie of the University, Paul Ehrlich Str. 23, D-67663 Kaiserlautem, Germany 'ORSTOM-UR-45 (Institut Françias de Recherche Scientifique pour le Développement en Coopération), Casilla de Correo 97, Asuncion, Paraguay Seventeen extracts and seven secondary metabolitesisolated from basidiomyceteswere tested in medi? culture against promastigote forms of Leishmania spp. and bloodstream forms of Trypanosoma cruzi. Extracts-from the culture filtrate or mycelium were generally inactive against the parasites except the Zucoagan'cus genus mycelium extract which reduced by 47% the number of bloodstream forms. Striatin A, striatin B and podoscyphic acid exhibited in vitro activity at 10,s and 100 pglmL, respectively. One compound showed activity against bloodstream forms of Z cruzi, the sesquiterpenoid naematolin, lysing the parasites by 79%. BALBk mice infected with L. amazonensis were treated 3 weeks post-infection with striatin A and striatin B by subcutaneous route for 15 days at 10 mgkg daily. The reference drug, N-methylglucamine antimonate, administered by subcutaneous injections at 28mg Sbv/kg/day for 15 days reduced the parasite burden by 71.2% (pe0.05). Subcutaneous administration of straitin A at 10 mgkg produced a weak decrease of the parasite burdens in the footpad by 17.6%. The treatment with striatin B had no effect and showed higher toxicity than striatinA. O 1997 by John Wiley & Sons, Ltd. Phytother. Res. 11, 193-197, 1997 (No. of Figures: 2. No. of Tables: 3. Keywords: basidiomycetes; Leiskmaizra; Trypaiiosoma cruzi; BALBlc mice; sesquiterpene;diterpene. No. of Refs: 12.) INTRODUCTION Diseases caused by protozoa, such as Leishmania sp. and Trypanosonia cruzi, are responsible for considerable mortal- ity and morbidity throughout the world, especially in the tropics of South America. In Paraguay, we established a programme to identify new active drugs, principally natural compounds for the treat- mént of cutaneous leishmaniasis and Chagas' disease. The Instituto de Investigaciones en Ciencias de la Salud (IICS), the French Institute of Scientific Research for the Develop- ment in Cooperation and the Laboratory of Biotechnology of the University of Kaiserslautern in Germany have initiated a study to evaluate the protozoal activity of secondary metabolites isolated from basidiomycetes. The basidiomycetes (mushrooms) constitute a class of fungi with an estimated number of 30000 species whose secondary metabolism and biologically active compounds have scarcely been investigated (Anke, 1989). The present work, the in vitro leishmanicidal (promastigote forms) and in vitro trypanocidal (bloodstream forms) effect of 14 species of basidiomycetes and seven secondary metabolites was evaluated by described methods (Fournet et al., 1994). The test against ?: cruzi was selected because of the excellent results obtained in experimental prophylactic additions stimulating blood (Rojas de Arias et al., 1994). Also, we tested two diterpenoids isolated from Gyathus * Correspondence to: A. Rojas de Arias. CCC 0951-418X/97/030193-05 O 1997 by John Wiley & Sons,ILtd. I 1 O 10010459 striatus (Hecht et al., 1978) on Leishinania amazonensis infected BALBk mice comparing their efficacy with a reference drug, N-methylglucamine antimonate (Glucan- time@). MATERIALS AND METHODS Isolation and chemistry Compounds tested. The extracts of basidiomycetes were supplied by Professor T. Anke, LB-Biotechnologie der Universität Kaiserslautern, Germany. The preparation of culture filtrate and mycelium from basidiomyctes was described by Anke (1989). The strains are deposited in the culture collection of the LB Biotechnologie, University of Kaiserslautern, Germany. The secondary metabolites from basidiomycetes (see Fig. 1 and Table 2) were isolated as described; aleurodiscal from Aleurodiscus inirabilis (Berk. & Curt.) Höhn) (Lauer et al., 1989), mniopetal E from Mniopetalum sp. 87256 (Kusche1 et al., 1994; Velten et al., 1994), naematolin from Hypholoina species (Backens et al., 1984), oosporein from Cordyceps A66-89 (Anke, 1989), podoscyphic acid from Pofoxypha species (Erkel et al., 1991), striatin A and striatin B from Cyathus striatus (Hecht et al., 1978). I Accepied I4 Ociober I996 Il I Fonds Documentaire ORSTOM