Investigating the antimalarial action of 1,2,4-trioxolanes with fluorescent chemical probes

Journal of Medicinal Chemistry

Volumn 54, Issue 23, 2011, Pages 8207-8213

  Hartwig, Carmony L ^a,b   Lauterwasser, Erica M W ^c   Mahajan, Sumit S ^c   Hoke, Jonathan M ^a   Cooper, Roland A ^a,d   Renslo, Adam R ^c  

^a OLD DOMINION UNIVERSITY   (United States)

^b AMERICAN TYPE CULTURE COLLECTION   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d DOMINICAN UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1,2,4 TRIOXOLANE DERIVATIVE; 4 OXOADAMANTAN 1 YL 5 (DIMETHYLAMINO)NAPHTHALENE 1 SULFONATE; 5 [DIMETHYLAMINO N [3 [DISPIRO(ADAMANTANE 2,2' [1,3,5]TRIOXOLANE 4',1'' CYCLOHEXANE) 4'' YL]AMINO]PROPYL]NAPHTHALENE 1 SULFONAMIDE; ANTIMALARIAL AGENT; CARBON; CYCLOHEXANE; DISPIRO(ADAMANTANE 2,2' [1,3,5]TRIOXOLANE 4',1'' CYCLOHEXANE) 5 YL 5 (DIMETHYLAMINO)NAPHTHALENE 1 SULFONATE; DISPIRO(ADAMANTANE 2,2' [1,3]DIOXOLANE 4',1'' CYCLOHEXANE) 5 YL 5 (DIMETHYLAMINO)NAPHTHALENE 1 SULFONATE; LIPID; TERT BUTYL N [3 [[DISPIRO(ADAMANTANE 2,2' [1,3,5]TRIOXOLANE 4',1'' CYCLOHEXANE) 4'' YL]AMINO]PROPYL]CARBAMATE; UNCLASSIFIED DRUG;

ANTIMALARIAL ACTIVITY; ANTIMALARIAL DRUG SUSCEPTIBILITY; ARTICLE; CELL VACUOLE; DRUG STRUCTURE; DRUG SYNTHESIS; FLUORESCENCE MICROSCOPY; HUMAN; HUMAN CELL; LIPID PEROXIDATION; NONHUMAN; PLASMODIUM FALCIPARUM; RING OPENING;

ADAMANTANE; ANTIMALARIALS; ARYLSULFONATES; FLUORESCENT DYES; HUMANS; LIPID PEROXIDATION; NAPHTHALENES; PARASITIC SENSITIVITY TESTS; PEROXIDES; PLASMODIUM FALCIPARUM; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 82555187385     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm2012003     Document Type: Article

References (32)

1. Guidelines for the Treatment of Malaria; World Health Organization: Geneva, 2006.
2. Ro, D. K.; Paradise, E. M.; Ouellet, M.; Fisher, K. J.; Newman, K. L.; Ndungu, J. M.; Ho, K. A.; Eachus, R. A.; Ham, T. S.; Kirby, J.; Chang, M. C.; Withers, S. T.; Shiba, Y.; Sarpong, R.; Keasling, J. D. Production of the antimalarial drug precursor artemisinic acid in engineered yeast Nature 2006, 440, 940-943
3. O'Neill, P. M.; Posner, G. H. A medicinal chemistry perspective on artemisinin and related endoperoxides J. Med. Chem. 2004, 47, 2945-2964
4. Vennerstrom, J. L.; Arbe-Barnes, S.; Brun, R.; Charman, S. A.; Chiu, F. C. K.; Chollet, J.; Dong, Y.; Dorn, A.; Hunziker, D.; Matile, H.; McIntosh, K.; Padmanilayam, M.; Santo Tomas, J.; Scheurer, C.; Scorneaux, B.; Tang, Y.; Urwyler, H.; Wittlin, S.; Charman, W. N. Identification of an antimalarial synthetic trioxolane drug development candidate Nature 2004, 430, 900-904
5. Charman, S. A.; Arbe-Barnes, S.; Bathurst, I. C.; Brun, R.; Campbell, M.; Charman, W. N.; Chiu, F. C.; Chollet, J.; Craft, J. C.; Creek, D. J.; Dong, Y.; Matile, H.; Maurer, M.; Morizzi, J.; Nguyen, T.; Papastogiannidis, P.; Scheurer, C.; Shackleford, D. M.; Sriraghavan, K.; Stingelin, L.; Tang, Y.; Urwyler, H.; Wang, X.; White, K. L.; Wittlin, S.; Zhou, L.; Vennerstrom, J. L. Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria Proc. Natl. Acad. Sci. U.S.A. 2011, 108, 4400-4405
6. O'Neill, P. M.; Barton, V. E.; Ward, S. A. The molecular mechanism of action of artemisinin-the debate continues Molecules 2010, 15, 1705-1721
7. Tang, Y.; Dong, Y.; Wang, X.; Sriraghavan, K.; Wood, J. K.; Vennerstrom, J. L. 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. 2005, 70, 5103-5110
8. Kaiser, M.; Wittlin, S.; Nehrbass-Stuedli, A.; Dong, Y.; Wang, X.; Hemphill, A.; Matile, H.; Brun, R.; Vennerstrom, J. L. Peroxide bond-dependent antiplasmodial specificity of artemisinin and OZ277 (RBx11160) Antimicrob. Agents Chemother. 2007, 51, 2991-2993
9. Eckstein-Ludwig, U.; Webb, R. J.; van Goethem, I. D. A.; East, J. M.; Lee, A. G.; Kimura, M.; O'Neill, P. M.; Bray, P. G.; Ward, S. A.; Krishna, S. Artemisinins target the SERCA of Plasmodium falciparum Nature 2003, 424, 957-961
10. Fugi, M. A.; Wittlin, S.; Dong, Y.; Vennerstrom, J. L. Probing the antimalarial mechanism of artemisinin and OZ277 (arterolane) with nonperoxidic isosteres and nitroxyl radicals Antimicrob. Agents Chemother. 2010, 54, 1042-1046
11. Uhlemann, A. C.; Wittlin, S.; Matile, H.; Bustamante, L. Y.; Krishna, S. Mechanism of antimalarial action of the synthetic trioxolane RBX11160 (OZ277) Antimicrob. Agents Chemother. 2007, 51, 667-672
12. Cardi, D.; Pozza, A.; Arnou, B.; Marchal, E.; Clausen, J. D.; Andersen, J. P.; Krishna, S.; Moller, J. V.; le Maire, M.; Jaxel, C. Purified E255L mutant SERCA1a and purified PfATP6 are sensitive to SERCA-type inhibitors but insensitive to artemisinins J. Biol. Chem. 2010, 285, 26406-26416
13. del Pilar Crespo, M.; Avery, T. D.; Hanssen, E.; Fox, E.; Robinson, T. V.; Valente, P.; Taylor, D. K.; Tilley, L. Artemisinin and a series of novel endoperoxide antimalarials exert early effects on digestive vacuole morphology Antimicrob. Agents Chemother. 2008, 52, 98-109
14. Selmeczi, K.; Robert, A.; Claparols, C.; Meunier, B. Alkylation of human hemoglobin A0 by the antimalarial drug artemisinin FEBS Lett. 2004, 556, 245-248
15. Robert, A.; Benoit-Vical, F.; Claparols, C.; Meunier, B. The antimalarial drug artemisinin alkylates heme in infected mice Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 13676-13680
16. Creek, D. J.; Charman, W. N.; Chiu, F. C.; Prankerd, R. J.; Dong, Y.; Vennerstrom, J. L.; Charman, S. A. Relationship between antimalarial activity and heme alkylation for spiro- and dispiro-1,2,4-trioxolane antimalarials Antimicrob. Agents Chemother. 2008, 52, 1291-1296
17. Haynes, R. K.; Chan, W. C.; Lung, C. M.; Uhlemann, A. C.; Eckstein, U.; Taramelli, D.; Parapini, S.; Monti, D.; Krishna, S. The Fe2+-mediated decomposition, PfATP6 binding, and antimalarial activities of artemisone and other artemisinins: the unlikelihood of C-centered radicals as bioactive intermediates ChemMedChem 2007, 2, 1480-1497
18. Klonis, N.; Crespo-Ortiz, M. P.; Bottova, I.; Abu-Bakar, N.; Kenny, S.; Rosenthal, P. J.; Tilley, L. Artemisinin activity against Plasmodium falciparum requires hemoglobin uptake and digestion Proc. Natl. Acad. Sci. U.S.A. 2011, 108, 11405-11410
19. Kannan, R.; Sahal, D.; Chauhan, V. S. Heme-artemisinin adducts are crucial mediators of the ability of artemisinin to inhibit heme polymerization Chem. Biol. 2002, 9, 321-332
20. Hartwig, C. L.; Rosenthal, A. S.; D'Angelo, J.; Griffin, C. E.; Posner, G. H.; Cooper, R. A. Accumulation of artemisinin trioxane derivatives within neutral lipids of Plasmodium falciparum malaria parasites is endoperoxide-dependent Biochem. Pharmacol. 2009, 77, 322-336
21. Hoang, A. N.; Sandlin, R. D.; Omar, A.; Egan, T. J.; Wright, D. W. The neutral lipid composition present in the digestive vacuole of Plasmodium falciparum concentrates heme and mediates beta-hematin formation with an unusually low activation energy Biochemistry 2010, 49, 10107-10116
22. Bousejra-El Garah, F.; Wong, M. H.-L.; Amewu, R. K.; Muangnoicharoen, S.; Maggs, J. L.; Stigliani, J.-L.; Park, B. K.; Chadwick, J.; Ward, S. A.; O'Neill, P. M. Comparison of the reactivity of antimalarial 1,2,4,5-tetraoxanes with 1,2,4-trioxolanes in the presence of ferrous iron salts, heme, and ferrous iron salts/phosphatidylcholine J. Med. Chem. 2011, 54, 6443-6455
23. Stocks, P. A.; Bray, P. G.; Barton, V. E.; Al-Helal, M.; Jones, M.; Araujo, N. C.; Gibbons, P.; Ward, S. A.; Hughes, R. H.; Biagini, G. A.; Davies, J.; Amewu, R.; Mercer, A. E.; Ellis, G.; O'Neill, P. M. Evidence for a common non-heme chelatable-iron-dependent activation mechanism for semisynthetic and synthetic endoperoxide antimalarial drugs Angew. Chem., Int. Ed. 2007, 46, 6278-6283
24. Tang, Y.; Dong, Y.; Karle, J. M.; DiTusa, C. A.; Vennerstrom, J. L. Synthesis of tetrasubstituted ozonides by the Griesbaum coozonolysis reaction: diastereoselectivity and functional group transformations by post-ozonolysis reactions J. Org. Chem. 2004, 69, 6470-6473
25. O'Neill, P. M.; Rawe, S. L.; Borstnik, K.; Miller, A.; Ward, S. A.; Bray, P. G.; Davies, J.; Oh, C. H.; Posner, G. H. Enantiomeric 1,2,4-trioxanes display equivalent in vitro antimalarial activity versus Plasmodium falciparum malaria parasites: Implications for the molecular mechanism of action of the artemisinins ChemBioChem 2005, 6, 2048-2054
26. Smilkstein, M.; Sriwilaijaroen, N.; Kelly, J. X.; Wilairat, P.; Riscoe, M. Simple and inexpensive fluorescence-based technique for high-throughput antimalarial drug screening Antimicrob. Agents Chemother. 2004, 48, 1803-1806
27. Bennett, T. N.; Paguio, M.; Gligorijevic, B.; Seudieu, C.; Kosar, A. D.; Davidson, E.; Roepe, P. D. Novel, rapid, and inexpensive cell-based quantification of antimalarial drug efficacy Antimicrob. Agents Chemother. 2004, 48, 1807-1810
28. Jackson, K. E.; Klonis, N.; Ferguson, D. J.; Adisa, A.; Dogovski, C.; Tilley, L. Food vacuole-associated lipid bodies and heterogeneous lipid environments in the malaria parasite, Plasmodium falciparum Mol. Microbiol. 2004, 54, 109-122
29. Pisciotta, J. M.; Coppens, I.; Tripathi, A. K.; Scholl, P. F.; Shuman, J.; Bajad, S.; Shulaev, V.; Sullivan, D. J., Jr. The role of neutral lipid nanospheres in Plasmodium falciparum haem crystallization Biochem. J. 2007, 402, 197-204
30. 11-BODIPY(581/591), an oxidation-sensitive fluorescent lipid peroxidation probe: (micro)spectroscopic characterization and validation of methodology Free Radical Biol. Med. 2002, 33, 473-490
31. Vennerstrom, J. L.; Dong, Y.; Charman, S. A.; Wittlin, S.; Chollet, J.; Wang, X.; Sriraghavan, K.; Zhou, L.; Matile, H.; Charman William, N. Spiro and dispiro 1,2,4-trioxolane antimalarials. Patent WO/2009/091433, 2009.
32. Fringuelli, F.; Germani, R.; Pizzo, F.; Savelli, G. One-Pot two-step synthesis of 1,2-diol Synth. Commun. 1989, 19, 1939-1943