ABSTRACT The activity of nerolidol, a sesquiterpene used as food-flavoring agent and currently under testing skin penetration enhancer for the transdermal delivery therapeutic drugs, was evaluated against Leishmania species. Nerolidol inhibited growth amazonensis , L. braziliensis chagasi promastigotes amastigotes with in vitro 50% inhibitory concentrations 85, 74, 75, 67 μM, respectively. treatment -infected macrophages 100 μM nerolidol resulted 95% reduction infection rates. Inhibition...

ABSTRACT Development of new drugs is one the strategies for malaria control. The biosynthesis several isoprenoids in Plasmodium falciparum was recently described. Interestingly, some intermediates and final products biosynthesized by this pathway mammals differ from those P. . These facts prompted us to evaluate various terpenes, molecules with a similar chemical structure pathway, as potential antimalarial drugs. Different terpenes S -farnesylthiosalicylic acid were tested on cultures...

Two genes encoding the enzymes 1-deoxy-D-xylulose-5-phosphate synthase and reductoisomerase have been recently identified, suggesting that isoprenoid biosynthesis in Plasmodium falciparum depends on methylerythritol phosphate (MEP) pathway, fosmidomycin could inhibit activity of reductoisomerase. The metabolite is not only an intermediate MEP pathway for isopentenyl diphosphate but also involved thiamin (vitamin B1) pyridoxal B6) plants many microorganisms. Herein we report first isolation...

Carotenoids are widespread lipophilic pigments synthesized by all photosynthetic organisms and some nonphotosynthetic fungi bacteria. All carotenoids derived from the C40 isoprenoid precursor geranylgeranyl pyrophosphate, their chemical physical properties associated with light absorption, free radical scavenging, antioxidant activity. generally in well defined subcellular organelles, plastids, which also present phylum Apicomplexa, comprises a number of important human parasites, such as...

Although the existence of O-linked oligosaccharide residues in glycoproteins Plasmodium falciparum has been shown, N-linked is still a matter controversy and skepticism.This report demonstrates unequivocal presence P. falciparum, principally ring young trophozoite stages intraerythrocytic cycle. These lose their capacity to bind concanavalin A-Sepharose after treatment cultures with tunicamycin under conditions that do not affect protein synthesis. When were treated N-Glycanase®,...

The cell-surface iodinatable proteins of Trypanosoma cruzi have been analyzed by two-dimensional polyacrylamide gel electrophoresis under equilibrium conditions. Antigenic polypeptides were characterized after immunoprecipitation and glycoproteins identified means lectin-affinity chromatography. Two glycoproteins, with affinity for concanavalin A, found to be common both infective (trypomastigote) non-infective (epimastigote) forms: protein 1 (90 kDa, pI 5.5-6.5) 2 (80 5.3-6.3). In...

Herein, we show that intraerythrocytic stages of Plasmodium falciparum have an active pathway for biosynthesis menaquinone. Kinetic assays confirmed plasmodial menaquinone acts at least in the electron transport. Similarly to Escherichia coli , observed increased levels parasites kept under anaerobic conditions. Additionally, mycobacterial inhibitor synthesis Ro 48‐8071 also suppressed and growth parasites, although off‐targets may play a role this growth‐inhibitory effect. Due its absence...

Malaria, an infectious disease that kills more than 438,000 people per year worldwide, is a major public health problem. The emergence of strains resistant to conventional therapeutic agents necessitates the discovery new drugs. We previously demonstrated various substances, including terpenes, have antimalarial activity in vitro and vivo. Nerolidol sesquiterpene present as essential oil several plants used scented products has been approved by US Food Drug Administration food-flavouring...

N-glycosylation of proteins is required for the intra-erythrocytic schizogony Plasmodium falciparum. In eukaryotic cells, this process involves transfer oligosaccharides from a dolichyl pyrophosphate derivative to asparagine residues. We have identified dolichol, phosphate and species 11 12 isoprenoid residues by metabolic labelling with [(3)H]farnesyl pyrophosphate, [(3)H]geranylgeranyl [(14)C]acetate in different stages P. This first demonstration short-chain dolichols phylum Apicomplexa....

ABSTRACT Isoprenylation is an essential protein modification in eukaryotic cells. Herein, we report that Plasmodium falciparum , a number of proteins were labeled upon incubation intraerythrocytic forms with either [ 3 H]farnesyl pyrophosphate or H]geranylgeranyl pyrophosphate. By thin-layer chromatography, showed attached isoprenoids are partially modified to dolichol and other, uncharacterized, residues, confirming active isoprenoid metabolism this parasite. Incubation blood-stage P....

The inhibition of farnesyltransferase was recently suggested as a new strategy for malaria therapy. A class inhibitors such 1 has been prepared which have in vivo activity murine model. These significantly reduce the farnesylation parasite proteins.

"The Isotype Composition and Avidity of Naturally Acquired Anti-Plasmodium falciparum Antibodies: Differential Patterns in Clinically Immune Africans Amazonian Patients" published on Sep 1996 by The American Society Tropical Medicine Hygiene.

Little is known about isoprenoid biosynthesis in parasitic protozoa. The presence of dolichol and isoprenylated proteins has been detected Plasmodium falciparum, but no studies are available the isoprenic side chain attached to benzoquinone ring coenzyme Q. In present study, using metabolic labelling with different intermediates, we demonstrated an active pathway for Our results show that P. falciparum able synthesize homologs (coenzyme Q8 Q9), depending on given intermediate. Parasites...

The 2-C-methyl-d-erythritol-4-phosphate and shikimate pathways were found to be active in Plasmodium falciparum both can result vitamin E biosynthesis plants algae. This study biochemically confirmed the malaria parasite, which inhibited by usnic acid. Furthermore, we evidence pointing a role of this infected erythrocytes. These findings not only contribute current understanding P. biology but also reveal pathway that could serve as chemotherapeutic target.

Abstract Background Isoprenoids are the most diverse and abundant group of natural products. In Plasmodium falciparum , isoprenoid synthesis proceeds through methyl erythritol diphosphate pathway products further metabolized by farnesyl synthase (FPPS), turning this enzyme into a key branch point synthesis. Changes in FPPS activity could alter flux compounds downstream and, hence, play central role regulation number essential functions parasites. Methods The isolation cloning gene...

Plasmodium falciparum is sensitive to oxidative stress in vitro and vivo, many drugs such as artemisinin, chloroquine cercosporin interfere the parasite's redox system. To minimize damage caused by reactive radicals, antioxidant enzymes their substrates found parasites erythrocytes must be functionally active. It was shown that P. synthesizes vitamin E usnic acid acts an inhibitor of its biosynthesis. Vitamin a potent protects polyunsaturated fatty acids from lipid peroxidation, this...

A proposed treatment for malaria is a combination of fosmidomycin and clindamycin. Both compounds inhibit the methylerythritol 4-phosphate (MEP) pathway, parasitic source farnesyl geranylgeranyl pyrophosphate (FPP GGPP, respectively). FPP GGPP are crucial biosynthesis several essential metabolites such as ubiquinone dolichol, well protein prenylation. Dietary prenols, farnesol (FOH) geranylgeraniol (GGOH), can rescue parasites from MEP inhibitors, suggesting existence missing pathway prenol...

Isoprenoids play important roles in all living organisms as components of structural cholesterol, steroid hormones mammals, carotenoids plants, and ubiquinones. Significant differences occur the length isoprenic side chains ubiquinone between different organisms, suggesting that enzymes are involved synthesis these chains. Whereas Plasmodium falciparum contain 7-9 units, 10-unit found humans. In a search for P. enzyme responsible biosynthesis attached to benzoquinone ring ubiquinones, we...