The antimalarial trioxaquine DU1301 alkylates heme in malaria-infected mice

Antimicrobial Agents and Chemotherapy

Volumn 52, Issue 8, 2008, Pages 2966-2969

  Garah, Fatima Bousejra El ^a   Claparols, Catherine ^a   Benoit Vical, Françoise ^a,b   Meunier, Bernard ^c   Robert, Anne ^a  

^a LCC LABORATOIRE DE CHIMIE DE COORDINATION   (France)

^b CHU RANGUEIL   (France)

^c Palumed   (France)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIMALARIAL AGENT; ARTEMISININ; CHLOROQUINE; DU 1301; HEME; UNCLASSIFIED DRUG;

ALKYLATION; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG STRUCTURE; LIQUID CHROMATOGRAPHY; MALARIA; MASS SPECTROMETRY; MOUSE; NONHUMAN; PLASMODIUM FALCIPARUM; PLASMODIUM VINCKEI; PRIORITY JOURNAL; SPLEEN;

ANIMALS; ANTIMALARIALS; CHROMATOGRAPHY, LIQUID; HEME; MALARIA; MASS SPECTROMETRY; MICE; MOLECULAR STRUCTURE; SESQUITERPENES;

EID: 48749099910     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/AAC.00165-08     Document Type: Article

References (25)

1. Asawamahasakda, W., I. Ittarat, Y.-M. Pu, H. Ziffer, and S. R. Meshnick. 1994. Reaction of antimalarial endoperoxide with specific parasite proteins. Antimicrob. Agents Chemother. 38:1854-1858.
2. Benoit-Vical, F., J. Lelièvre, A. Berry, C. Deymier, O. Dechy-Cabaret, J. Cazelles, C. Loup, A. Robert, J.-F. Magnaval, and B. Meunier. 2007. Trioxaquines are new antimalarial agents active on all erythrocytic forms, including gametocytes. Antimicrob. Agents Chemother. 51:1463-1472.
3. Bray, P. G., O. Janneh, K. J. Raynes, M. Mungthin, H. Ginsburg, and S. A. Ward. 1999. Cellular uptake of chloroquine is dependent on binding to ferriprotoporphyrin IX and is independent of NHE activity in Plasmodium falciparum. J. Cell Biol. 145:363-376.
4. Dechy-Cabaret, O., F. Benoit-Vical, C. Loup, A. Robert, H. Gornitzka, A. Bonhoure, H. Vial, J.-F. Magnaval, J.-P. Séguéla, and B. Meunier. 2004. Synthesis and antimalarial activity of trioxaquine derivatives. Chem. Eur. J. 10:1625-1636.
5. Egan, T. J., and H. M. Marques. 1999. The role of haem in the activity of chloroquine and related antimalarial drugs. Coord. Chem. Rev. 190-192:493-517.
6. Hong, Y.-L., Y.-Z. Yang, and S. R. Meshnick. 1994. The interaction of artemisinin with malarial hemozoin. Mol. Biochem. Parasitol. 63:121-128.
7. Ittarat, W., A. L. Pickard, P. Rattanasinganchan, P. Wilairatana, S. Looareesuwan, K. Emery, J. Low, R. Udomsangpetch, and S. R. Meshnick. 2003. Recrudescence in artesunate-treated patients with falciparum malaria is dependent on parasite burden not on parasite factors. Am. J. Trop. Med. Hyg. 68:147-152.
8. Jefford, C. W. 2007. New developments in synthetic peroxidic drugs as artemisinin mimics. Drug Discov. Today 12:487-495.
9. Jefford, C. W., F. Favarger, V. H. Maria da Graca, and Y. Jacquier. 1995. The decomposition of cis-fused cyclopenteno-1,2,4-trioxanes by ferrous salts and some oxophilic reagents. Helv. Chim. Acta 78:452-458.
10. Jefford, C. W., A. Jaber, and J. Boukouvalas. 1989. The regio- and stereocontrolled synthesis of cis-p-menth-3-ene-1,2-diol by means of a 1,2,4-trioxane intermediate. J. Chem. Soc. Chem. Commun. 1989:1916-1918.
11. Laurent, S. A.-L., C. Loup, S. Mourgues, A. Robert, and B. Meunier. 2005. Heme alkylation by artesunic acid and trioxaquine DU1301, two antimalarial trioxanes. Chembiochem 6:653-658.
12. Loup, C., J. Lelièvre, F. Benoit-Vical, and B. Meunier. 2007. Trioxaquines and heme-artemisinin adducts inhibit the in vitro formation of hemozoin better than chloroquine. Antimicrob. Agents Chemother. 51:3768-3770.
13. Meunier, B. 2008. Hybrid molecules with a dual mode of action: dream or reality? Acc. Chem. Res. 41:69-77.
14. Moreau, S., B. Perly, C. Chachaty, and C. Deleuze. 1985. A nuclear magnetic resonance study of the interactions of antimalarial drugs with porphyrins. Biochim. Biophys. Acta 840:107-116.
15. O'Neill, P. M., and G. H. Posner. 2004. A medicinal perspective on artemisinin and related endoperoxides. J. Med. Chem. 47:2945-2964.
16. Peters, W., J. H. Portus, and B. L. Robinson. 1975. Chemotherapy of rodent malaria. XXII. Value of drug-resistant strains of Plasmodium berghei in screening for blood schizontocidal activity. Ann. Trop. Med. Parasitol. 69:155-171.
17. Posner, G. H., C. H. Ho, D. Wang, L. Gerena, W. K. Milhous, S. R. Meshnick, and W. Asawamahasakda. 1994. Mechanism-based design, synthesis, and in vitro antimalarial testing of new 4-methylated trioxanes structurally related to artemisinin: the importance of a carbon-centered radical for antimalarial activity. J. Med. Chem. 37:1256-1258.
18. Robert, A., F. Benoit-Vical, C. Claparols, and B. Meunier. 2005. The antimalarial drug artemisinin alkylates heme in infected mice. Proc. Natl. Acad. Sci. USA 102:13676-13680. (Erratum, 103:3943, 2006.)
19. Robert, A., and B. Meunier. 1997. Characterization of the first covalent adduct between artemisinin and a heme model. J. Am. Chem. Soc. 119:5968-5969.
20. Schenck, G. O., and K. Ziegler. 1944. Die Synthese des Ascaridols. Naturwissenschaften 32:157.
21. Sullivan, D. J., Jr., I. Y. Gluzman, D. G. Russel, and D. E. Goldberg. 1996. On the molecular mechanism of chloroquine's antimalarial action. Proc. Natl. Acad. Sci. USA 93:11865-11870.
22. Tang, Y., Y. Dong, and J. L. Vennerstrom. 2004. Synthetic peroxides as antimalarials. Med. Res. Rev. 24:425-448.
23. Tang, Y., Y. Dong, X. Wang, K. Sriraghavan, J. K. Wood, and J. L. Vennerstrom. 2005. Dispiro-1,2,4-trioxane analogues of a prototype dispiro-1,2,4-trioxolane: mechanistic comparators for artemisinin in the context of reaction pathways with iron(II). J. Org. Chem. 70:5103-5110.
24. White, N. J. 2008. Qinghaosu (artemisinin): the price of success. Science 320:330-334.
25. Wongsrichanalai, C., A. L. Pickard, W. H. Wernsdorfer, and S. R. Meshnick. 2002. Epidemiology of drug-resistant malaria. Lancet Infect. Dis. 2:209-218.