Antimalarial flavonoids, antifungal pyrones and hexalobines from three annonaceae species

The investigations reported in this Thesis were aimed at phytochemical analysis for biologically active and other natural products from three plants of the family annonaceae, namely Uvaria dependens, Sanrfoelia ruffanammari and Hexalobus monopetalus. Phytochemical investigations of Uvaria dependens were carried but on fruits collected from Magoroto, East Usambara Mountains in Muheza district, Tanga region. The methanol extract yielded one unreported, 5,6,7-trimethoxyflav-3-ene and two known flavonoids, 5,7,8-trimethoxflay-3-ene and 6’-hydroxy-2’,3’4’- trimethoxychalcone. The compounds exhibited mild antimalarial activity against the multi-drug resistant K1 strain of Plasmodium falciparum in vitro, with 〖IC〗_50 values of 9 and 5 ug/ml, respectively. The 5,7,8-trimethoxyflav-3-ene previously isolated from the stem bark of U. dependens was also pbtained from the fruits in these investigations. Phytochemical screening of the ethanol extract of the root bark extract of Sanrafaelia ruddonanunari collected from Kwamngumi Forest Reserve in the northern foothills of the East Usambara Mountains in Muheza District, Tanzania region, yielded the two styrylpyrones (+)-6-styry1-7,8-dihydroxy-4-methoxypyran-2-one and a hitherto unreported enantiomer (-)-6-styry-7,8-dihydrones exhibited antifungal activity against Candida albicans, with zones of inhibition of 17 and 9 mm, respectively, at a concentration of 100 ug/ml. a cyclopropane derivative was also isolated from the root bark but the structure is still not established due to inadequate spectral information which was available at the time of writing this thesis. Chemical analysis of the ethanol extract of the fruits of Hexalobus monopetalus collected from Ugowola village in Tabora district, Tabora region, gave three known and one hitherto unreported diprenylated indole of the hexalobine type. These were 3.5-hexalobine C, 3.5-hexalobine D, 3-(2’,3’-(dihydroxy-3’-methylbutyl)-5-(3”-methyl-crotonoyl)indole and the hitherto unreported ester 5-(2”,3”-epoxy-3”-methylbuty)-3-(3’-hydroxy-3’-methylbut-2-yl)-5-(3”-methylcrotonoyl)indole exhibited antifungal activity against Candida albicans at a concentration of 100 ug/ml, with zones of inhibition of 14 and 5 mm respectively, indicating that the latter compound was only mildly active. Regarding the ester 5-(2”,3”-epoxy-3”-methylbuty)-3-(3’-hydroxy-3’-methyl-1’-acetyloxybut-2’-y1)indole, the question arose as to whether it could be regarded as a genuine natural product or an artifact, being formed through transesterification of the corresponding diol in the presence of acidic ethyl acetate used in the isolation process. However, such acidic conditions would also favour the opening of the epoxide ring on the second prenyl group. Furthermore, a diol of this compound was not formed when the ester was re-subjected to the isolation conditions using the same ethyl acetate as before. It was therefore concluded that this compound is a genuine natural product and not an artefact.