Publication Title: 
The Journal of Antibiotics

Antimalarial screening was performed for microbial metabolites that simulate artemisinin in their mode of action, a potent antimalarial component of an herbal remedy with a characteristic peroxide structure. Nanaomycin A was identified in this screen as an antimalarial compound, together with radicicol and several other compounds already reported (J. Antibiotics 51: 153 approximately 160, 1998). Nanaomycin A inhibited in vitro growth of the human malaria parasite Plasmodium falciparum with an IC80 value of 33.1 nM. It was as potent as radicicol and about 1/10 as potent as artemisinin.

Tanaka, Y.
Kamei, K.
Otoguro, K.
Omura, S.
Publication Title: 
FEBS letters

Fourier transform infrared (FTIR) and resonance Raman (RR) spectroscopies have been employed to investigate the reductive cleavage of the O-O bond of the endoperoxide moiety of the antimalarial drug artemisinin and its analog trioxane alcohol by hemin dimer. We have recorded FTIR spectra in the nu(O-O) and nu(as)(Fe-O-Fe) regions of artemisinin and of the hemin dimer that show the cleavage of the endoperoxide and that of the hemin dimer, respectively. We observed similar results in the trioxane alcohol/hemin dimer reaction.

Kapetanaki, S.
Varotsis, C.
Publication Title: 
Protein Science: A Publication of the Protein Society

Glutathione S-transferase of the malarial parasite Plasmodium falciparum (PfGST) represents a novel class of GST isoenzymes. Since the architecture of the PfGST substrate binding site differs significantly from its human counterparts and there is only this one isoenzyme present in the parasite, PfGST is considered a highly attractive target for antimalarial drug development. Here we report the mechanistic, kinetic, and structural characterization of PfGST as well as its interaction with different ligands.

Hiller, Nicole
Fritz-Wolf, Karin
Deponte, Marcel
Wende, Wolfgang
Zimmermann, Herbert
Becker, Katja
Publication Title: 
Biochemical Pharmacology

Artemisinin loses its antimalarial activity on prolonged exposure to erythrocytes, especially alpha-thalassemic erythrocytes. In this report, we show that the major artemisinin-inactivating factor in cytosol of normal erythrocytes was heat-labile but a heat-stable factor from alpha-thalassemic cells also played a significant role in reducing artemisinin effectiveness, which was shown to be heme released from hemoglobin (Hb).

Ponmee, Napawan
Chuchue, Tatsanee
Wilairat, Prapon
Yuthavong, Yongyuth
Kamchonwongpaisan, Sumalee
Publication Title: 
Biological & Pharmaceutical Bulletin

Artemisinin exerts the antimalarial activity through activation by heme. The hemolysis in malaria results in the elevated levels of plasma heme which may affect the activity of artemisinin. We hypothesized that the extracellular heme would potentiate the antimalarial activity of artemisinin. Hemin (ferric heme) at the pathologic concentrations enhanced the activity of artemisinin against Plasmodium falciparum in vitro and increased the levels of the lipid peroxidation products in the presence of artemisinin.

Tangnitipong, Sunanta
Thaptimthong, Thitiporn
Srihirun, Sirada
Unchern, Supeenun
Kittikool, Dusadee
Udomsangpetch, Rachanee
Sibmooh, Nathawut
Publication Title: 
PloS One

BACKGROUND: Hemozoin crystals are normally formed in vivo by Plasmodium parasites to detoxify free heme released after hemoglobin digestion during its intraerythrocytic stage. Inhibition of hemozoin formation by various drugs results in free heme concentration toxic for the parasites. As a consequence, in vitro assays have been developed to screen and select candidate antimalarial drugs based on their capacity to inhibit hemozoin formation.

Thomas, Vincent
Góis, Ana
Ritts, Bruce
Burke, Peter
Hänscheid, Thomas
McDonnell, Gerald
Publication Title: 

A central problem in biology is to identify gene function. One approach is to infer function in large supergenomic networks of interactions and ancestral relationships among genes; however, their analysis can be computationally prohibitive. We show here that these biological networks are compressible. They can be shrunk dramatically by eliminating redundant evolutionary relationships, and this process is efficient because in these networks the number of compressible elements rises linearly rather than exponentially as in other complex networks.

Lisewski, Andreas Martin
Quiros, Joel P.
Ng, Caroline L.
Adikesavan, Anbu Karani
Miura, Kazutoyo
Putluri, Nagireddy
Eastman, Richard T.
Scanfeld, Daniel
Regenbogen, Sam J.
Altenhofen, Lindsey
Llinás, Manuel
Sreekumar, Arun
Long, Carole
Fidock, David A.
Lichtarge, Olivier
Publication Title: 
International Journal of Molecular Medicine

Although hepatitis C virus (HCV) affects approximately 130-170 million people worldwide, no vaccines are available. HCV is an important cause of chronic hepatitis, cirrhosis and hepatocellular carcinoma, leading to the need for liver transplantation. In this study, curcumin, a constituent used in traditional Chinese medicine, has been evaluated for its anti-HCV activity and mechanism, using a human hepatoma cell line containing the HCV genotype 1b subgenomic replicon.

Chen, Ming-Ho
Lee, Ming-Yang
Chuang, Jing-Jing
Li, Yi-Zhen
Ning, Sin-Tzu
Chen, Jung-Chou
Liu, Yi-Wen
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