Fitoquímica, quimiossistemática e busca de novos fármacos antichagásicos e antileishmanioses: estudo de Raputia praetermissa (Rutaceae).

Abstract

Raputia praetermissa (Engler) Emmerich is a tree found only in the Forest Reserve Adolpho Ducke, Amazonas, Brazil. The genus Raputia was originally described by Engler and many species were included in this genus, but in 1978, Emmerich proposed three new genera Neoraputia, Raputiarana e Sigmathantus in order to accommodate six species, four belonging to the genus Raputia, which is assigned into the tribe Cuspariae, and two that had not been described yet. From our knowledge no previous phytochemical work has been reported on Raputia. Therefore, this study describes phytochemical and chemosystematic investigation and the search of compounds with trypanocidal and leishmanicidal activity from roots of R. praetermissa. The phytochemical work involved crude extract preparation, followed by fractionation and isolation of compounds thorough different chromatography methods. Spectroscopic analyses permitted the identification of them and the results showed the presence of new substances in addition to those isolated previously. Here we reported the isolation and identification of the new compounds: two new limonoids, 11β,19α-dihydroxi-7- deoxo-7-acetoxy-ichangin e 11β,19α-oxide-7-deacetoxy-7-hidroxy-ichangin, two new prenylated indoles alkaloids, 5-[(3 -dimethylalil-4 -methylidene)-2 -tetrahidrofuran-2 - il]-indol e 5-[(4 -carbomethoxy)-furan-2 -il]-indol and a new bisindol alkaloid, 5 ,6 -[5- methyl-5(7-indol-5 -il-etene-6,7-diil)-3(1-methylprop-2-en-2-il)]-ciclopentane-5 ,6 -diilindol. The following known substances were also obtained: T-cadinol, β-sitosterol, stigmasterol, campesterol, 3-[2 ,6 -dimethoxy-6 ,6 -dimethylpyrano(2 ,3 :3 ,4 ) phenyl]-methylpropionate, 3-oxo-cadinol, lanosta-7,24-dien-21-oic acid-3-oxo, dictamine, γ-fagarine, 1-methyl-4-methoxy-2-quinolone, tricoccin S13 acetate, 6- formylindol. Our results showed that the chemical classes isolated from R. praetermissa roots are common to the Rutaceae family, but the prenylated indol alkaloids are not. These compounds are new classes of prenylated indol alkaloids. However, all isolated compounds confirm the assigned it into the tribe Cuspariae. In addition, the compounds were evaluated for: a) in vitro biological activity against trypanosomastigotes forms of Trypanosoma cruzi and amastigotes forms of Leishmania braziliensis; b) enzymatic inhibitory activity on glyceraldehydes- XXXII phospato-dehidrogenase (gGAPDH) of T. cruzi and enzymatic inhibitory activity on adenine-phosphoribosyl-transferase (APRT) of Leishmania tarentolae. None of isolated substances were promising against T. cruzi in vitro test as well as in enzymatic experimental models (gGAPDH e APRT) from which they not showed enzymatic inhibitory activity. Conversely, the T-cadinol was active against L. braziliensis and results in DL50 44 µM.