Constituants chimiques et activités antiparasitaires de Beilschmiedia louisii Robyns & R. Wilczek, Beilschmiedia obscura Engl. et Persea americana Mill (Lauraceae). Structures, synthèse de quelques dérivés de l’acide beilschmiedique E.

Abstract

The present work deals with the chemical investigation and the evaluation of the antiplasmodial and antitrypanosomal activities of three Cameroonian plant species: Beilschmiedia louisii, Beilschmiedia obscura and Persea americana (Lauraceae). These three plants are used in traditional medicine for the treatment of parasitic diseases and whose extracts showed potent antitrypanosomal and antiplasmodial activities during the preliminary screening in vitro. The phytochemical investigation, using usual chromatographic methods, led to the isolation of twenty-six compounds among which twenty-two have been fully characterized with different spectroscopic techniques of analysis (UV, IR, MS, 1D and 2D NMR) and by comparison of some physical and spectral data with those described in the literature. Four of these compounds are new and isolated for the first time from a natural source [two endiandric acid derivatives (beilschmiedol B and beilschmiedol C), an alkene (obscurene A) and an alcohol (perseatriol)]. The eighteen other characterized compounds belong to eight classes of natural substances, among which: four flavonoids (epicatechin, kaempferol-3-O-α-L- (3″ E, 4″ E-di-pcoumaroyl)-rhamnoside , isoquercitrin, astragalin), two steroids (β-sitosterol, β-sitosterol 3-O-β-D-glucopyranoside), a coumarin (scopoletin), a lignan (9,9′-di-O-feruloyl-5, 5′-dimethoxysecoisolariciresinol), one alkene (pentacosan-1-ene), five endiandric acids (beilschmiedic acid A, beilschmiedic acid C, 3˝, 4˝-methylenedioxyendiandric acid A, beilschmiedic acid D, beilschmidic acid (E), one carotene (lutein), two γ-lactones (3-hydroxy- 4-methyl-2- (13′-phenyl-1ʹ-n-tridecyl) -butanolide and 3 -hydroxy-4-methyl-2- (11ʹ-phenyl-1ʹ- n-undecyl) -butanolide) and a phenylalkanoic acid (15-phenylpentadecanoic acid). The last three compounds are isolated for the first time from the genus Beilschmiedia. From beislmiedic acid E, four semisynthetic derivatives have been prepared by reduction, oxidation and nucleophilic addition reactions. These derivatives have been named as bielschmiedol A, beischmiedal, bielschmiecarbazone and beilschmiegallate. Isolated and semi-synthetic compounds have also been evaluated for their antitrypanosomal and antiplamodial activities. Among the tested compounds, the mixture of beilschmiedols B / C and β-sitosterol and the mixture of 3-hydroxy-4-methyl-2- (13'-phenyl-1'- n- tridecyl) -butanolide and 3-hydroxy-4-methyl-2- (11'-phenyl- 1'-n-undecyl) –butanolide showed the best antitrypanosomal activities with IC50 <10 μg/mL whereas the semisynthesis derivatives showed moderate activities on the same strain. Beilschmiedol A showed low activity on T.b. bucei with an IC50 value of 20.38 μg/mL. Regarding antimalarial activity, 9,9′-di-O-feruloyl-5,5′-dimethoxysecoisolariciresinol kaempferol-3-O-α-L- (3″E,4″E-di-p-coumaroyl) - rhamnoside and lutein exhibited very good activities with IC50 values of 0.04, 0.63 and 2.5 μg/mL while persiatriol showed moderate activity with the IC50 value of 9.5 μg/mL. The most interesting compounds, 9,9′-di-O-feruloyl- 5,5′-dimethoxysecoisolariciresinol (bilignane IC50 = 0,04 μg / mL) and kaempferol-3-O-α-L-(3″E,4″E-di-p-coumaroyl)-rhamnoside flavonoïd (IC50 = 0,63 μg / mL) were as active as the reference drug, chloroquine and not cytotoxic. The extracts and compounds were also evaluated for their cytotoxicity on human carcinoma cells (HeLa Cells). Extracts and compounds isolated from Beilschmiedia were found to be inactive, whereas those from the roots and leaves of Persea americana were shown to be cytotoxic with IC50 values <6.00 μg/mL. Among the active compounds, only persiatriol showed low selectivity (SI = 0.34). These results contribute to the chemotaxonomy and to the valorization of B. louisii, B. obscura and of P. americana in folk medecine in the treatment of parasitic diseases. B. louisii and B. obscura are also new sources of endiandric acids. .