Activity of selected phytochemicals against Plasmodium falciparum.

According to the WHO, in 2008, there were 247 million reported cases of malaria and nearly one million deaths from the disease. Parasite resistance against first-line drugs, including artemisinin and mefloquine, is increasing. In this study the plant-derived compounds aglafolin, rocaglamid, kokusaginine, arborine, arborinine and tuberostemonine were investigated for their anti-plasmodial activity in vitro.

Anti-leishmanial activity of plant-derived acridones, flavaglines, and sulfur-containing amides.

Visceral and cutaneous leishmaniases are an important public health problem in endemic geographic regions in 88 countries worldwide, with around 12 million infected people. Treatment options are limited due to toxicity and teratogenicity of the available drugs, response problems in HIV/Leishmania co-infections, and upcoming resistances. In this study, we investigated the anti-leishmanial activity of 13 plant-derived compounds in vitro aiming to find new drug candidates.

High antitrypanosomal activity of plant-derived sulphur-containing amides.

Chagas disease, caused by Trypanosoma cruzi, represents an important public health problem in endemic geographic regions in Middle and South America, affecting 15 million infected people. Treatment options are still limited due to the toxicity of available drugs, parasite resistance and poor drug activity during the chronic phase of the disease. In this study, we investigated the in vitro antitrypanosomal activity of 15 tropical plant-derived compounds with the aim of finding new drug candidates.

Antitumor activity and mechanism of action of the cyclopenta[b]benzofuran, silvestrol.

Background: Flavaglines are a family of natural products from the genus Aglaia that exhibit anti-cancer activity in vitro and in vivo and inhibit translation initiation. They have been shown to modulate the activity of eIF4A, the DEAD-box RNA helicase subunit of the eukaryotic initiation factor (eIF) 4F complex, a complex that stimulates ribosome recruitment during translation initiation. One flavagline, silvestrol, is capable of modulating chemosensitivity in a mechanism-based mouse model.

Therapeutic suppression of translation initiation modulates chemosensitivity in a mouse lymphoma model.

Disablement of cell death programs in cancer cells contributes to drug resistance and in some cases has been associated with altered translational control. As eukaryotic translation initiation factor 4E (eIF4E) cooperates with c-Myc during lymphomagenesis, induces drug resistance, and is a genetic modifier of the rapamycin response, we have investigated the effect of dysregulation of the ribosome recruitment phase of translation initiation on tumor progression and chemosensitivity. eIF4E is a subunit of eIF4F, a complex that stimulates ribosome recruitment during translation initiation by delivering the DEAD-box RNA helicase eIF4A to the 5' end of mRNAs.

Pyrrolo- and pyridoazepine alkaloids as chemical markers in Stemona species.

Broad-based phytochemical investigations on 31 Stemona species and geographical provenances led to an overview concerning characteristic accumulation trends and the distribution of different Stemona alkaloids. Two major metabolic differences suggested a taxonomic segregation of the complex Stemona tuberosa group from the other species, and was supported by morphological characters. Whereas most of the Stemona species were characterised by protostemonine type alkaloids, the S.

Development of a pharmacodynamic screening model with Entamoeba histolytica.

Human amoebiasis caused by Entamoeba histolytica is widely distributed in the tropics and subtropics, but also occurring in neighbouring parts of the temperate zones. Invasive amoebiasis causes dysentery and, by haematogenous spread, also extra-intestinal hepatic, pulmonary or cerebral abscesses, not rarely fatal conditions. The available anti-amoebic drugs have shortcomings regarding tolerability and efficacy.

Development of a pharmacodynamic screening model with Crithidia fasciculata.

The genus Crithidia is a member of the family Trypanosomatidae and is related to the genera Leishmania and Trypanosoma with which it shares a variety of biochemical mechanisms, such as polyamine synthesis and methionin salvage. In consequence, a screening system for antiparasitic candidate material has been developed with Crithidia fasciculata, a parasite naturally occurring in insects and amphibians, but devoid of pathogenicity for humans. Initially a variety of culture media were evaluated of which TPS was best suited for the maintenance of stock cultures, and E-medium - a newly developed formula - for sensitivity testing.

Antioxidant dehydrotocopherols as a new chemical character of Stemona species.

From the roots of various Stemona species four new dehydrotocopherols (chromenols) were isolated and their structures and stereochemistry elucidated by spectroscopic methods. The double bond between C-3 and C-4 proved to be a typical chemical character of the genus found in most of the species. Various C-methylations of the aromatic ring reflect differences in methyltransferase activities and agreed with the current species delimitations showing an exclusive accumulation of dehydro-delta-tocopherol for the Stemona tuberosa group, whereas different provenances of Stemona curtisii were characterized by dehydro-gamma-tocopherol accompanied by small amounts of dehydro-alpha-tocopherol.

Activity of novel plant extracts against medullary thyroid carcinoma cells.

Background: Medullary thyroid carcinoma (MTC) is a rare calcitonin-producing tumor, derived from the parafollicular C-cells of the thyroid. MTC is known to be relatively insensitive to conventional chemotherapy.

Materials And Methods: Eight cell lines were established from MTCs; each showed an up-regulation of Bcl-2.

Feeding deterrence and contact toxicity of Stemona alkaloids-a source of potent natural insecticides.

On the basis of chronic feeding bioassays with neonate larvae of Spodoptera littoralis reared on an artificial diet, the methanolic leaf and root extracts from Stemona collinsae displayed very high insect toxicity compared to those of two Aglaia species, a commercial Pyrethrum extract, and azadirachtin, whereas S. tuberosa extracts demonstrated low activity in roots and no activity in leaves. Beyond that, in leaf disk choice tests against fifth instar larvae, S.