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ANTI-L DONOVANI ACTIVITY IN MACROPHAGE/AMASTIGOTE MODEL OF PALMARUMYCIN CP18 AND ITS LARGE SCALE PRODUCTION
Autor
Afiliación
University of Panama. Faculty of Natural Exact Sciences and Technology. Laboratory of Tropical Bioorganic Chemistry. Republic of Panama/Smithsonian Tropical Research Institute. USA
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratorio de Pesquisas Clinicas. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratorio de Pesquisas Clinicas. Belo Horizonte, MG, Brasil
Smithsonian Tropical Research Institute. USA
Smithsonian Tropical Research Institute. USA
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratorio de Pesquisas Clinicas. Belo Horizonte, MG, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratorio de Pesquisas Clinicas. Belo Horizonte, MG, Brasil
Smithsonian Tropical Research Institute. USA
Smithsonian Tropical Research Institute. USA
Resumen en ingles
Palmarumycin CP18, isolated from an extract of the fermentation broth and mycelium of the Panamanian endophytic fungus Edenia sp., was previously reported with strong and specific activity against Leishmania donovani. Here we report that when the same strain was cultured on different solid media--Harrold Agar, Leonian Agar, Potato dextrose Agar (PDA), Corn Meal Agar, Honey Peptone Agar, and eight vegetables (V8) Agar--in order to determine the optimal conditions for isolation of palmarumycin CP18, no signal for this compound was observed in any of the 1H NMR spectra of fractions obtained from these extracts. However, one extract, prepared from the fungal culture in PDA contained significant amounts of CJ-12,372, a possible biosynthetic precursor of palmarumycin CP18. Edenia sp. was cultivated on a large scale on PDA and CJ-12,372 was converted to palmarumycin CP18 by oxidation of its p-hydroquinone moiety with DDQ in dioxane. Palmarumycin CP18 showed anti-leishmanial activity against L. donovani in a macrophage/amastigote model, with IC50 values of 23.5 microM.
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