Chemical investigations and evaluation of antisamonella properties of a cameroonian medicinal plant: detarium microcarpum guill. et perr. (Caesalpiniaceae).

Abstract

Typhoid fever is a disease caused by a microbe of the specie Salmonella enterica. It causes a lot of damage in the world. The remedy used to treat this disease is ciprofloxacin. But these salmonellas have developed forms of resistance to these remedies, hence the need to seek new therapeutic agents. The use of plants in traditional medecine suggest that they contain bioactive molecules that can be used in the treatment of this disease. This thesis reports the phytochemical investigation of a cameroonian medicinal plant: Detarium microcarpum Guill. Perr. (Caesalpiniaceae) and the antisalmonella assay of the hydroethanolic extracts, fractions and some isolated compounds. Twenty-five compounds were obtained from the procedures described in this work, and eighteen were fully characterized among which three new derivatives. The method used for the isolation of the compounds was mainly column chromatography. Structure elucidation was achieved mainly by NMR spectroscopy including IR spectroscopy, mass spectrometry and 1D and 2D-NMR (COSY,HMQC, HMBC and NOESY). A bio-guided investigation of the methanolic and hydroethanolic extracts of the fruits of D. microcarpum led to the isolation and the characterization of ten compounds while the hydroethanolic extracts of root bark and root wood afforded eight compounds. They belong to six classes of natural substances and were classified as follows: Three diterpenoids: one of the clerodane type known as (4aR, 5S, 6R, 8aR) 5-(carboxymethyl)-5,6,8a-trimethyl-3,4,4a,5,6,7,8,8a-octahydronaphthalene-1-carboxylic acid 118 and two of the labdane type, including a new one to which the trivial name microcarpin 116 was assigned and another known as rhinocerotinoic acid 117, One new cyanogenic derivative to which we assigned the name Microcarposide 114, One new ceramide to which the trivial name microcarpamide 115 has been assigned, One xanthone : 1,7-dihydroxy-6-methylxanthone 129, Two flavonoids: luteolin 131 and epicatechin 132, Five pentacyclic triterpenes: ursolic acid 123, alphitolic acid 121, betulinic acid 120, 3 , 24 -dihydroxylup-20 (29) -en-28-oic acid 122 and lupeol 119 all known,Four phytosterols: -sitosterol 128 and its 3-O- -D-glucopyranoside derivative 125, stigmasterol 127 and its 3-O- -D-glucopyranoside derivative 126 and the mixture of -sitosterol and stigmasterol 124, One phenolic compound: methyl gallate 130 Crystallographicdata of acid (4aR, 5S, 6R, 8aR)-5-(carboxymethyl)-5,6,8a-trimethyl-3,4,4a,5,6,7,8,8a-octahydronaphthalene- 1-carboxylic and microcarpine are presented here for the first time. Rhinocerotonoic acid has been transformed to its hydroxylated derivative with the aim of studying its structure activity relationship. Microcarposide, rhinocerotinoic acid and microcarpamide exhibited moderate antisalmonella activity in vitro against three strains namely S. typhi, S. enteritidis and S. typhimurium with a MIC values of 62.5, 31.25, and 31.25 g/mL, respectively. The results of in vitro and in vivo tests on the same Salmonella strains with a MIC value of 1.95 g/mL, in addition to the low acute and subacute toxicity of the hydro-ethanolic root-bark extract obtained, allowed us to perform a pre-formulation of a phyto-drug in the form of a syrup, to be used for the treatment of typhoid fever.