JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Pandey, A. V.
Right arrow Articles by Chauhan, V. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Pandey, A. V.
Right arrow Articles by Chauhan, V. S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

J Biol Chem, Vol. 274, Issue 27, 19383-19388, July 2, 1999

Artemisinin, an Endoperoxide Antimalarial, Disrupts the Hemoglobin Catabolism and Heme Detoxification Systems in Malarial Parasite

Amit V. PandeyDagger , Babu L. Tekwani§, Ram L. Singh, and Virander S. ChauhanDagger

From the Dagger  Malaria Research Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, P. O. Box 10504, New Delhi 110 067, the § Division of Biochemistry, Central Drug Research Institute, Lucknow 226 001, and the  Department of Biochemistry, R.M.L. Avadh University, Faizabad 224 001, India

Endoperoxide antimalarials based on the ancient Chinese drug Qinghaosu (artemisinin) are currently our major hope in the fight against drug-resistant malaria. Rational drug design based on artemisinin and its analogues is slow as the mechanism of action of these antimalarials is not clear. Here we report that these drugs, at least in part, exert their effect by interfering with the plasmodial hemoglobin catabolic pathway and inhibition of heme polymerization. In an in vitro experiment we observed inhibition of digestive vacuole proteolytic activity of malarial parasite by artemisinin. These observations were further confirmed by ex vivo experiments showing accumulation of hemoglobin in the parasites treated with artemisinin, suggesting inhibition of hemoglobin degradation. We found artemisinin to be a potent inhibitor of heme polymerization activity mediated by Plasmodium yoelii lysates as well as Plasmodium falciparum histidine-rich protein II. Interaction of artemisinin with the purified malarial hemozoin in vitro resulted in the concentration-dependent breakdown of the malaria pigment. Our results presented here may explain the selective and rapid toxicity of these drugs on mature, hemozoin-containing, stages of malarial parasite. Since artemisinin and its analogues appear to have similar molecular targets as chloroquine despite having different structures, they can potentially bypass the quinoline resistance machinery of the malarial parasite, which causes sublethal accumulation of these drugs in resistant strains.

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Antimicrob. Agents Chemother.Home page
M. del Pilar Crespo, T. D. Avery, E. Hanssen, E. Fox, T. V. Robinson, P. Valente, D. K. Taylor, and L. Tilley
Artemisinin and a Series of Novel Endoperoxide Antimalarials Exert Early Effects on Digestive Vacuole Morphology
Antimicrob. Agents Chemother., January 1, 2008; 52(1): 98 - 109.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
H. C. Hoppe, D. A. van Schalkwyk, U. I. M. Wiehart, S. A. Meredith, J. Egan, and B. W. Weber
Antimalarial Quinolines and Artemisinin Inhibit Endocytosis in Plasmodium falciparum
Antimicrob. Agents Chemother., July 1, 2004; 48(7): 2370 - 2378.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
S. R. Meshnick, R. K. Haynes, D. Monti, D. Taramelli, N. Basilico, S. Parapini, and P. Olliaro
Artemisinin and Heme
Antimicrob. Agents Chemother., August 1, 2003; 47(8): 2712 - 2713.
[Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
R. K. Haynes, D. Monti, D. Taramelli, N. Basilico, S. Parapini, and P. Olliaro
Artemisinin Antimalarials Do Not Inhibit Hemozoin Formation
Antimicrob. Agents Chemother., March 1, 2003; 47(3): 1175 - 1175.
[Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
F. Dzierszinski, A. Coppin, M. Mortuaire, E. Dewailly, C. Slomianny, J.-C. Ameisen, F. DeBels, and S. Tomavo
Ligands of the Peripheral Benzodiazepine Receptor Are Potent Inhibitors of Plasmodium falciparum and Toxoplasma gondii In Vitro
Antimicrob. Agents Chemother., October 1, 2002; 46(10): 3197 - 3207.
[Abstract] [Full Text] [PDF]

Home page
 J Antimicrob ChemotherHome page
B. Pradines, J. M. Rolain, F. Ramiandrasoa, T. Fusai, J. Mosnier, C. Rogier, W. Daries, E. Baret, G. Kunesch, J. Le Bras, et al.
Iron chelators as antimalarial agents: in vitro activity of dicatecholate against Plasmodium falciparum
J. Antimicrob. Chemother., August 1, 2002; 50(2): 177 - 187.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
J. Bhisutthibhan and S. R. Meshnick
Immunoprecipitation of [3H]Dihydroartemisinin Translationally Controlled Tumor Protein (TCTP) Adducts from Plasmodium falciparum-Infected Erythrocytes by Using Anti-TCTP Antibodies
Antimicrob. Agents Chemother., August 1, 2001; 45(8): 2397 - 2399.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 1999 by the American Society for Biochemistry and Molecular Biology.