In this study the in vitro antiplasmodial activities of extracts from Cussonia spicata (Araliaceae), Artemisia afra, Vernonia colorata, V. natalensis (Asteraceae), Parinari curatellifolia (Chrysobalanaceae), Clutia hirsuta, Flueggea virosa, (Euphorbiaceae), Adenia gummifera (Passifloraceae) and Hymenodictyon floribundum, (Rubiaceae) were evaluated. The lipophilic extracts from the aerial parts of Artemisia afra and Vernonia colorata proved to be the most active against the chloroquine-sensitive strain PoW and against the chloroquine-resistant clone Dd2 of Plasmodium falciparum. Bioassay-guided fractionation of the extract of A. afra yielded seven flavonoids, from which acacetin, genkwanin and 7-methoxyacacetin showed in vitro activity; the IC(50) values ranged from 4.3 microgram/mL to 12.6 microgram/mL. In addition, several sesquiterpene lactones could be obtained from the most active fractions. Whereas eudesmaafraglaucolide proved to be inactive, the guaianolides 1-desoxy-1alpha-peroxy-rupicolin A-8-O-acetate, 1alpha,4alpha-dihydroxybishopsolicepolide and rupicolin A-8-O-acetate revealed in vitro antiplasmodial activity. Evaluation of V. colorata gained four sesquiterpenes 11beta,13-dihydrovernodalin, vernodalol, 11beta,13-dihydrovernolide and 11beta,13,17,18-tetrahydrovernolide, from which the first two constituents exhibited the strongest antiplasmodial activity (IC(50) values: 1.1-4.8 microgram/mL).

Saponin Targeted toxin A B S T R A C TTumor-targeting protein toxins are composed of a toxic enzyme coupled to a specific cell binding domain that targets cancer-associated antigens. The anti-tumor treatment by targeted toxins is accompanied by dose-limiting side effects. The future prospects of targeted toxins for therapeutic use in humans will be determined by reduce side effects. Certain plant secondary metabolites (saponins) were shown to increase the efficacy of a particular epidermal growth factor receptor (EGFR)-targeted toxin, paralleled by a tremendous decrease of side effects.This study was conducted in order to investigate the effects of substituting different toxin moieties fused to an EGF ligand binding domain on the augmentative ability of saponins for each against therapeutic potential of the saponin-mediated efficacy increase for different anti-tumor toxins targeting the EGFR.We designed several EGFR-targeted toxins varying in the toxic moiety. Each targeted toxin was used in combination with a purified saponin (SA1641), isolated from the ornamental plant Gypsophila paniculata L. SA1641 was characterized and the SA1641-mediated efficacy increase was investigated on EGFR-transfected NIH-3T3 cells.We observed a high dependency of the SA1641-mediated efficacy increase on the nature of toxin used for the construction of the targeted toxin, indicating high specificity.Structural alignments revealed a high homology between saporin and dianthin-30, the two toxic moieties that benefit most from the combination with SA1641.We further demonstrate that SA1641 did not influence the plasma membrane permeability,

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uated. From the lipophilic extract of C. tenuifolia five active flavones were obtained. 4Ј,5-Dihydroxy-7-methoxyflavone [genkwanin] and 5-hydroxy-4Ј,7-dimethoxyflavone [apigenin 4Ј,7-dimethylether] exhibited the strongest antiplasmodial activity against a chloroquine-sensitive strain (poW) and a chloroquine-resistant strain (Dd2) of Plasmodium falciparum (IC 50 values: 17.1Ð28.5 µm). Furthermore octadeca-9,12-dienoic acid [linoleic acid] {IC 50 values of 21.8 µm (poW) and 31.1 µm (Dd2)} and octadeca-9,12,15-trienoic acid (α-linolenic acid) were isolated.

The results demonstrate for the first time the ability of chalcone derivatives to interfere with the haemin-degradation process of P. falciparum. This effect might contribute to their antiplasmodial activity. Nevertheless, as one compound showed inhibition of P. falciparum without being able to interact with GSH-dependent haemin degradation, other modes of action must add to the observed antiparasitic activity of hop chalcones.

SummaryThe in vitro antiplasmodial activities of 14 plant species traditionally used in Central America for the treatment of malaria or fever were evaluated. Lipophilic extracts of Piper hispidum, Siparuna andina, S. pauciflora, S. tonduziana, and Xylopia cf. frutescens, proved to be active against both a chloroquine-sensitive and a resistant strain of Plasmodium falciparum. IC 50 values ranged between 3.0 g/ml and 21.9 g/ml; however, moderate cytotoxicity of active extracts was observed. Bioactivity-guided fractionation of Piper hispidum yielded 2Ј,4,6Ј-trihydroxy-4Ј-methoxydihydrochalcone (asebogenin) as an active compound.

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