Etude chimique guidée par CL-SM et par l’activité antileishmaniale de Vernonia guineensis Benth (Asteraceae) : Essai de standardisation et pré-formulation de phytomédicaments

Abstract

An extensive chemical and biological study of Vernonia guineensis Benth. (Asteraceae) led to isolation and caracterization of 34 compounds with 3 new derivatives, viz: - Three ceramides: vernoguinamide (73) a new derivative, elasticamide (74) and (2S, 3S, 4R) -2-N - [(2′R) -hydroxyhexacosanoyl]-4-hydroxysphinganine (75); - Four anthraquinones: physcion (76), erythroglaucin (77), revandchinone-3 (78) and emodin (79); - Three flavonoids: vernoguinoflavone (80) a new derivative, quercetin (11) and luteolin (14); - Two glycerol ester derivatives: bisarachidicester (81) a naturally isolated for the first and 2,3-dihydroxypropyl heptacosanoate (82); - Two sesquiterpenes: vernopicrin (52) and vernomelitensin (53); - Six steroids: vernoguinoside A (42) and vernoguinoside (44), β-sitosterol 3-O-β-D-glucoside (83), stigmasterol 3-O-β-D-glucoside (84), stigmastérol (85) and β-sitostérol (86); - Six triterpenoids: hop-17(21)-en-3b-yl acetate (87) (isolated for the first time from the Asteraceae family), lupeol (33), betulinic acid (88), β-amyrin (36), oleanolic acid (37) and ursolic acid (38). - Two carotenoids: 13-cis-β-carotène (89) and β-carotène (90); - Three fatty acids: tricosanoic acid (91), tetracosanoic acid (92), and pentacosanoic acid (93). - Three alcohol derivatives: docosan-1-ol (94), triacontan-1-ol (95) and heptatriacontan-1-ol (96). The compounds were isolated by chromatography and their structures were determined by interpretation of their physical data such as MS-ESI/IE, IR, UV, 1D (1H, 13C, DEPT) and 2D (HMQC, HMBC, 1H -1H COSY, NOESY) NMR, then by comparison with literature data and finally by chemical transformations. The biological study allowed the evaluation of the antileishmanial activity on the promastigote form of Leishmania donovani (1 S (MHOM/SD/62/1S). Antibacterial, antioxidant, cytotoxic and acute toxicity activities were also evaluated. The different samples tested showed relatively high activities on all targeted pathologies with a low toxicity threshold (IS >2). Indeed, the ranges of antileishmanial activity (IC50 evaluation) were between [50―0.33] μg/mL against 0.35 μg/mL for Amphotericin B (positive control). The ranges of antioxidant activity (IC50 evaluation) were [250-1] μg/mL, compared to [2―1] μg/mL for vitamin C (positive control). The ranges of antibacterial activity (MIC evaluation) were [2000―3.2] μg/mL, compared to [7.8―1.56] μg/mL for Ciprofloxacin (positive control). As a result of this work, a standardisation and preformulation trial of phytomedicines was carried out.