Etude chimique de quelques Entada (Mimosaceae) et Aframomum (Zingiberaceae): Potentiels trypanocides et bactericides.

Abstract

The present work is focused on the phytochemical study of plants of the genus Entada (E.) (Mimosaceae) and Aframomum (A.)(Zingiberaceae) which can be potential souces of new molecules with antiparasitic and antibacterial activities. Some species of these genuses are used in traditional medecine for the treatment of various ailments such as fever, rheumatic and abdominal pain, inflammation, bronchitis, gonorrhea, sleeping sickness. The phytochemical study of the bark of E. abyssinica led to the isolation of a new diterpene of kolavane series (15-methylester kolavic acid), a sterol (β-sitosterol) and a mixture of ten saturated fatty acids (C20-C29). The structures were determined by the interpretation of their NMR spectra (1D and 2D). From the bark of E. africana we isolate four pure compounds: 15-methylester kolavic acid, lupeol, β-sitosterol and octacosanoate of 2,3 dihydroxypropyl, and two mixtures: the first containing octacosanol, tetracosanoïc and hexacosanoïc acids and the second composed of three isomers of alkyl ferulic acid (C26, C28 et C30). The seeds of Aframomum daniellii gave us the major component aframodial which has been transformed into aframodiol by reduction. Analysis by Liquid Chromatography coupled to the High Pressure Mass Spectrometry (HPLC-MS) of seven species of Aframomum (A. melegueta, A. daniellii, A. citratum, A. sulcatum, A. pruinosum, A. letestuianum and A. kayserianum or A. latifolium) showed the presence of compounds 6-gingerol, 6-shogaol and 6-paradol only in the seeds of A. Melegueta while we found only 6-gingerol in the fruit pulp of A. melegueta and A. daniellii. We also found that 6-gingerol is more abundant in the hexane extract of the fruit pulp of A. daniellii at a concentration of 3.32μg / g. Inhibition tests carried out on the cells reveal that 15-methylester kolavic acid shows an IC50 of 1.7µM on the cells of Trypanosoma brucei and an IC50 > 32 µM on those of Leishmania infantum. Aframodial and aframodiol are non cytotoxiques. The enzyme inhibition test carried out on glycolytic enzymes revealed to us that 15- methylester kolavic acid inhibits pyruvate kinase (PyKs) enzyme of Leishmania Mexicana and Bacillus stearothermophillus. The most important results are those obtained from glyceraldehyde-3-phosphate deshydrogenase (GAPDH) and aldolase. In fact, it is 3 and 66 times more active on GAPDH of the parasites Trypanosoma brucei and Trypanosoma cruzi than that of the host; it inhibits 13 times more the aldolase of Trypanosoma brucei than the mammal. Aframodial is 2 times more active on the phosphoglucose isomérase (PGI) of Trypanosoma brucei than on its homologous in the host; it is 11 times more active on thealdolase of Trypanosoma brucei than on its homologous isolated from the muscle of a rabbit. Aframodiol activates the phosphoglycerate kinase (PGK) of Trypanosoma brucei, the phosphofructokinase (PFK) of rabbit muscle and the hexokinase of yeast; it is 2 times more active on the GAPDH of the rabbit’s muscle than on Trypanosoma brucei. The study of the enzymatic kinetic shows that aframodial is a mixt inhibitor of PyK of the rabbit’s muscle (Ki = 30 ± 2 µM; K’i = 65 ± 2 µM), and an uncompetitive inhibitor of the aldolase of Trypanosoma brucei (K’i = 22.5 ± 2 µM). The antibacterial tests carried out on isolated compounds show that octacosanoate of 2,3-dihydroxylpropyle is active on two strains of Escherichia coli. Aframodial is bactericidal on the NAE16 strain of Providencia stuartii. Aframodiol inhibits the growth of NAE16 P. stuarti’s and KP55 of K. pneumonia strains. The extracts of hexane, methylene chloride and methylene chloride/ methanol (1:1) of Entada africana are bactericidal on the AG100A Escherichia coli’s strain. Referred to what preceed, it is possible to establish a correlation between the use of these plants in traditional medicine and the trypanocidal and bactericidal activities showed.