Lipids as Drug Targets for Malaria Therapy

Apicomplexan Parasites: Molecular Approaches toward Targeted Drug Development

Volumn , Issue , 2011, Pages 137-162

  Vial, Henri J ^a   Penarete, Diana ^a   Wein, Sharon ^a   Caldarelli, Sergio ^a   Fraisse, Laurent ^b   Peyrottes, Suzanne ^c  

^a UNIVERSITÉ DE MONTPELLIER   (France)

^b SANOFI   (France)

^c UNIVERSITÉ DE MONTPELLIER   (France)

Author keywords

Antimalarials; Fatty acid; Lipid; Malaria; Pharmacology; Phosphatidylcholine; Phospholipid

Indexed keywords

EID: 84864421625     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9783527633883.ch8     Document Type: Chapter

References (96)

1. WHO (2008) World malaria report 2008. World Health Organization, Geneva, Switzerland http://www.who.int/malaria/wmr2008/.
2. WHO (2008) Roll Back Malaria, The Global Malaria Action Plan for a malariafree world. WHO, Geneva, Switzerland http://www.rollbackmalaria.org/gmap/index.html Geneva, p. 274.
3. Noedl, H., Socheat, D., and Satimai, W. (2009) Artemisinin-resistant malaria in Asia. N. Engl. J. Med., 361, 540-541.
4. Dondorp, A.M., Nosten, F., Yi, P., Das, D., Phyo, A.P. et al. (2009) Artemisinin resistance in Plasmodium falciparum malaria. N. Engl. J. Med., 361, 455-467.
5. Biagini, G.A., O'Neill, P.M., Nzila, A., Ward, S.A., and Bray, P.G. (2003) Antimalarial chemotherapy: young guns or back to the future' Trends Parasitol., 19, 479-487.
6. Biot, C. and Chibale, K. (2006) Novel approaches to antimalarial drug discovery. Infect. Disord. Drug Targets, 6, 173-204.
7. Schlitzer, M. (2007) Malaria chemotherapeutics part I: History of antimalarial drug development, currently used therapeutics, and drugs in clinical development.ChemMedChem,2,944-986.
8. Schlitzer, M. (2008) Antimalarial drugs - what is in use and what is in the pipeline. Arch. Pharm. (Weinheim), 341, 149-163.
9. Mazumdar, J. and Striepen, B. (2007) Make it or take it: fatty acid metabolism of apicomplexan parasites. Eukaryot. Cell, 6, 1727-1735.
10. Tarun, A.S., Vaughan, A.M., and Kappe, S.H. (2009) Redefining the role of de novo fatty acid synthesis in Plasmodium parasites. Trends Parasitol., 25, 545-550.
11. Salom-Roig, X.J., Hamze, A., Calas, M., and Vial, H.J. (2005) Dual molecules asnew antimalarials. Comb. Chem. High Throughput Screen, 8, 49-62.
12. Vial, H.J. and Calas, M. (2001) Inhibitors of phospholipid metabolism, in Antimalarial Chemotherapy,Mechanisms of Action, Modes of Resistance, and New Directions in Drug Development (ed. P. Rosenthal), Humana Press, Totowa, NJ, pp. 347-365.
13. Holz, G.G. (1977) Lipids and the malaria parasite. Bull. World Health Org., 55, 237-248.
14. Vial, H. and Ancelin, M. (1998) Malarial lipids, in Malaria: Parasite Biology, Biogenesis, Protection (ed. I. Sherman), ASMPress,Washington DC, pp. 159-175.
15. Vial, H. and Mamoun, C. (2005) Plasmodium lipids: metabolism and function, in Molecular Approach toMalaria (ed. I. Sherman), ASM Press,Washington DC, pp. 327-352.
16. Vial, H.J., Eldin, P., Tielens, A.G., and van Hellemond, J.J. (2003) Phospholipids in parasitic protozoa. Mol. Biochem. Parasitol., 126, 143-154.
17. Van Deenen, L.L.M. and De Gier, J. (1975) Lipids of the red cell membrane, in The Red BloodCell (ed. G. Surgenor),Academic Press, New York, pp. 147-211.
18. Vial, H.J. and Ancelin, M.L. (1992) Malarial lipids. An overview. Subcell. Biochem., 18, 259-306.
19. Vial, H.J., Ancelin, M.L., Philippot, J.R., and Thuet, M.J. (1990) Biosynthesis and dynamics of lipids in Plasmodium-infected mature mammalian erythrocytes. Blood Cells, 16, 531-555.
20. Coppens, I. and Vielemeyer, O. (2005) Insights into unique physiological features of neutral lipids in Apicomplexa: from storage to potential mediation in parasite metabolic activities. Int. J. Parasitol., 35, 597-615.
21. Lawrence, C.W. and Cenedella, R.J. (1969) Lipid content of Plasmodium bergheiinfected rat red blood cells. Exp. Parasitol., 26, 181-186.
22. Stocker, R. et al. (1987) Lipids from Plasmodium vinckei-infected erythrocytes and their susceptibility to oxidative damage. Lipids, 22, 51-57.
23. Grellier, P., Rigomier, D., Clavey, V., Fruchart, J.C., and Schrével, J. (1991) Lipid traffic between high density lipoproteins and Plasmodium falciparum-infected red blood cells. J. Cell Biol., 112, 267-277.
24. Ancelin, M.L., Parant, M., Thuet, M.J., Philippot, J.R., and Vial, H.J. (1991) Increased permeability to choline in simian erythrocytes after Plasmodium knowlesi infection. Biochem. J., 273 (Pt 3), 701-709.
25. Biagini, G.A., Pasini, E.M., Hughes, R., De Koning, H.P., and Vial, H.J. (2004) et al. Characterization of the choline carrier of Plasmodium falciparum: a route for the selective delivery of novel antimalarial drugs. Blood, 104, 3372-3377.
26. Kirk, K., Wong, H.Y., Elford, B.C., Newbold, C.I., and Ellory, J.C. (1991) Enhanced choline and Rb + transport in human erythrocytes infected with the malaria parasite Plasmodium falciparum. Biochem. J., 278 Pt (2), 521-525.
27. Ancelin, M.L. and Vial, H.J. (1986) Several lines of evidence demonstrating that Plasmodium falciparum, a parasitic organism, has distinct enzymes for the phosphorylation of choline and ethanolamine. FEBS Lett., 202, 217-223.
28. Ancelin, M.L. and Vial, H.J. (1986) Choline kinase activity in Plasmodiuminfected erythrocytes: characterization and utilization as a parasite-specific marker in malarial fractionation studies. Biochim. Biophys. Acta, 875, 52-58.
29. Ancelin, M.L., Vial, H.J., and Philippot, J.R. (1986) Characterization of choline and ethanolamine kinase activities in Plasmodium-infected erythrocytes, in Enzymes of Lipid Metabolism II (eds L. Freysz, H. Dreyfus, R. Massarelli, and S. Gatt), Plenum Press, New York.
30. Goldberg, D.E. (2005) Hemoglobin degradation. Curr. Top. Microbiol. Immunol., 295, 275-291.
31. Woodrow, C. and Krishna, S. (2005) Molecular Approaches toMalaria: Glycolysis in Asexual-Stage Parasites (ed. I.W. Sherman), ASM Press.
32. Beitz, E., Pavlovic-Djuranovic, S., Yasui, M., Agre, P., and Schultz, J.E. (2004) Molecular dissection of water and glycerol permeability of the aquaglyceroporin from Plasmodium falciparum by mutationalanalysis. Proc. Natl Acad. Sci. USA, 101, 1153-1158.
33. Hansen, M., Kun, J.F., Schultz, J.E., and Beitz, E. (2002) A single, bi-functional aquaglyceroporin in blood-stage Plasmodium falciparum malaria parasites. J. Biol. Chem., 277, 4874-4882.
34. Newby, Z.E., O'Connell, J. 3rd, Robles- Colmenares, Y., Khademi, S., Miercke, L.J., and Stroud, R.M. (2008) Crystal structure of the aquaglyceroporin PfAQP from the malarial parasite Plasmodium falciparum. Nat. Struct. Mol. Biol., 15, 619-625.
35. Schnick, C., Polley, S.D., Fivelman, Q.L., Ranford-Cartwright, L.C., Wilkinson, S.R., Brannigan, J.A., Wilkinson, A.J., and Baker, D.A. (2009) Structure and nonessential function of glycerol kinase in Plasmodium falciparum blood stages. Mol. Microbiol., 71, 533-545.
36. Promeneur, D., Liu, Y.,Maciel, J., Agre, P., King, L.S., and Kumar, N. (2007) Aquaglyceroporin PbAQP during intraerythrocytic development of the malaria parasite Plasmodium berghei. Proc. Natl Acad. Sci. USA, 104, 2211-2216.
37. Mitamura, T., Hanada, K., Ko-Mitamura, E.P., Nishijima, M., and Horii, T. (2000) Serum factors governing intraerythrocytic development and cell cycle progression of Plasmodium falciparum. Parasitol. Int., 49, 219-229.
38. Vielemeyer, O., McIntosh, M.T., Joiner, K.A., and Coppens, I. (2004) Neutral lipid synthesis and storage in the intraerythrocytic stages of Plasmodium falciparum. Mol. Biochem. Parasitol., 135, 197-209.
39. Vial, H.J., Thuet, M.J., Broussal, J.L., and Philippot, J.R. (1982) Phospholipid biosynthesis by Plasmodium knowlesiinfected erythrocytes: the incorporation of phospholipid precursors and the identification of previously undetected metabolic pathways. J. Parasitol., 68, 379-391.
40. Vial, H.J., Thuet, M.J., and Philippot, J.R. (1982) Phospholipid biosynthesis in synchronous Plasmodium falciparum cultures. J. Protozool., 29, 258-263.
41. Vial, H.J., Thuet, M.J., and Philippot, J.R. (1984) Cholinephosphotransferase and ethanolaminephosphotransferase activities in Plasmodium knowlesi-infected erythrocytes. Their use as parasite-specific markers. Biochim. Biophys. Acta, 795, 372-383.
42. Krishnegowda, G. and Gowda, D.C. (2003) Intraerythrocytic Plasmodium falciparum incorporates extraneous fatty acids to its lipids without any structural modification. Mol. Biochem. Parasitol., 132, 55-58.
43. Gratraud, P., Huws, E., Falkard, B., Adjalley, S., Fidock, D.A. et al. (2009) Oleic acid biosynthesis in Plasmodium falciparum: characterization of the stearoyl-CoA desaturase and investigation as a potential therapeutic target. PLoS One, 4, e6889.
44. Carman, G.M. and Henry, S.A. (1989) Phospholipid biosynthesis in yeast. Annu. Rev. Biochem., 58, 635-669.
45. Li, Z. and Vance, D.E. (2008) Phosphatidylcholine and choline homeostasis. J. Lipid Res., 49, 1187-1194.
46. Moll, G.N., Vial, H.J., Ancelin, M.L., Op den Kamp, J.A., Roelofsen, B., and van Deenen, L.L. (1988) Phospholipid uptake by Plasmodium knowlesi infected erythrocytes. FEBS Lett., 232, 341-346.
47. Elabbadi, N., Ancelin, M.L., and Vial, H.J. (1997) Phospholipid metabolism of serine in Plasmodium-infected erythrocytes involves phosphatidylserine and direct serine decarboxylation. Biochem. J., 324 Pt (2), 435-445.
48. Pessi, G., Choi, J.Y., Reynolds, J.M., Voelker, D.R., and Mamoun, C.B. (2005) In vivo evidence for the specificity of Plasmodium falciparum phosphoethanolamine methyltransferase and its coupling to the Kennedy pathway. J. Biol. Chem., 280, 12461-12466.
49. Pessi, G., Kociubinski, G., and Mamoun, C.B. (2004) A pathway for phosphatidylcholine biosynthesis in Plasmodium falciparum involving phosphoethanolamine methylation. Proc. Natl Acad. Sci. USA, 101, 6206-6211.
50. Witola,W.H., El Bissati, K., Pessi, G., Xie, C., Roepe, P.D., andMamoun, C.B. (2008) Disruption of the Plasmodium falciparum PfPMT gene results in a complete loss of References j159phosphatidylcholine biosynthesis via the serine-decarboxylasephosphoethanolamine-methyltransferase pathway and severe growth and survival defects. J. Biol. Chem., 283, 27636-27643.
51. Déchamps, S., Wengelnik, K., Berry-Sterkers, L., Cerdan, R., Vial, H.J., and Gannoun-Zaki, L. (2010) The Kennedy phospholipid biosynthesis pathways are refractory to genetic disruption in Plasmodium berghei and therefore appear essential in blood stages. Mol. Biochem. Parasitol., 173 (2), 69-80.
52. Dechamps, S., Maynadier, M., Wein, S., Gannoun-Zaki, L., Marechal, E., and Vial, H.J. (2009) Rodent and non-rodent malaria parasites differ in their phospholipid metabolic pathways. J. Lipid Res., 51 (1), 81-96.
53. Baunaure, F., Eldin, P., Cathiard, A.M., and Vial, H. (2004) Characterization of a non-mitochondrial type I phosphatidylserine decarboxylase in Plasmodium falciparum. Mol. Microbiol., 51, 33-46.
54. Rontein, D., Nishida, I., Tashiro, G., Yoshioka, K., Wu, W.I. et al. (2001) Plants synthesize ethanolamine by direct decarboxylation of serine using a pyridoxal phosphate enzyme. J. Biol. Chem., 276, 35523-35529.
55. Kent, C. (1995) Eukaryotic phospholipid biosynthesis. Annu. Rev. Biochem., 64, 315-343.
56. Witola,W.H. and BenMamoun, C. (2007) Choline induces transcriptional repression and proteasomal degradation of the malarial phosphoethanolamine methyltransferase. Eukaryot. Cell, 6, 1618-1624.
57. Alberge, B., Gannoun-Zaki, L., Bascunana, C., Tran van Ba, C., Vial, H., and Cerdan, R. (2010) Comparison of the cellular and biochemical properties of Plasmodium falciparum choline and ethanolamine kinases. Biochem. J., 425, 149-158.
58. Choubey, V., Guha, M., Maity, P., Kumar, S., and Raghunandan, R. (2006) et al. Molecular characterization and localization of Plasmodium falciparum choline kinase. Biochim. Biophys. Acta, 1760, 1027-1038.
59. Witola, W.H., Pessi, G., El Bissati, K., Reynolds, J.M., andMamoun, C.B. (2006) Localization of the phosphoethanolamine methyltransferase of the human malaria parasite Plasmodium falciparum to the Golgi apparatus. J. Biol. Chem., 281, 21305-21311.
60. Le Roch, K.G., Johnson, J.R., Ahiboh, H., Chung, D.W., Prudhomme, J. et al. (2008) A systematic approach to understand the mechanism of action of the bisthiazolium compound T4 on the human malaria parasite, Plasmodium falciparum. BMC Genomics, 9, 513.
61. Bakovic, M., Fullerton, M.D., and Michel, V. (2007)Metabolic and molecular aspects of ethanolamine phospholipid biosynthesis: the role of CTP: phosphoethanolamine cytidylyltransferase (Pcyt2). Biochem. Cell Biol., 85, 283-300.
62. Kent, C. (2005) Regulatory enzymes of phosphatidylcholine biosynthesis: a personal perspective. Biochim. Biophys. Acta, 1733, 53-66.
63. Vance, J.E. (1998) Eukaryotic lipidbiosynthetic enzymes: the same but not the same. Trends Biochem. Sci., 23, 423-428.
64. Ancelin, M.L. and Vial, H.J. (1989) Regulation of phosphatidylcholine biosynthesis in Plasmodium-infected erythrocytes. Biochim. Biophys. Acta, 1001, 82-89.
65. Gardner, M.J., Hall, N., Fung, E., White, O., Berriman, M. et al. (2002) Genome sequence of the human malaria parasite Plasmodium falciparum. Nature, 419, 498-511.
66. McFadden, G.I. and Roos, D.S. (1999) Apicomplexan plastids as drug targets. Trends Microbiol., 7, 328-333.
67. Surolia, N. and Surolia, A. (2001) Triclosan offers protection against blood stages of malaria by inhibiting enoyl-ACP reductase of Plasmodium falciparum. Nat. Med., 7, 167-173.
68. Carballeira, N.M. (2008) New advances in fatty acids as antimalarial, antimycobacterial and antifungal agents. Prog. Lipid Res., 47, 50-61.
69. Yu, M., Kumar, T.R., Nkrumah, L.J., Coppi, A., Retzlaff, S. et al. (2008) The fatty 160j 8 Lipids as Drug Targets for Malaria Therapyacid biosynthesis enzyme FabI plays a key role in the development of liver-stage malarial parasites. Cell Host Microbe, 4, 567-578.
70. Vaughan, A.M., O'Neill, M.T., Tarun, A.S., Camargo, N., Phuong, T.M. et al. (2009) Type II fatty acid synthesis is essential only for malaria parasite late liver stage development. Cell Microbiol., 11, 506-520.
71. Vial, H.J., Thuet, M.J., Ancelin, M.L., Philippot, J.R., and Chavis, C. (1984) Phospholipid metabolism as a new target for malaria chemotherapy. Mechanism of action of D-2-amino-1-butanol. Biochem. Pharmacol., 33, 2761-2770.
72. Kumaratilake, L.M., Robinson, B.S., Ferrante, A., and Poulos, A. (1992) Antimalarial properties of n-3 and n-6 polyunsaturated fatty acids: in vitro effects on Plasmodium falciparum and in vivo effects on P. berghei. J. Clin. Invest., 89, 961-967.
73. Krugliak, M., Deharo, E., Shalmiev, G., Sauvain, M., Moretti, C., andGinsburg, H. (1995) Antimalarial effects of C18 fatty acids on Plasmodium falciparum in culture and on Plasmodium vinckei petteri and Plasmodium yoelii nigeriensis in vivo. Exp. Parasitol., 81, 97-105.
74. Beaumelle, B.D. and Vial, H.J. (1988) Correlation of the efficiency of fatty acid derivatives in suppressing Plasmodium falciparum growth in culture with their inhibitory effect on acyl-CoA synthetase activity. Mol. Biochem. Parasitol., 28, 39-42.
75. Ancelin, M.L. and Vial, H.J. (1986) Quaternary ammonium compounds efficiently inhibit Plasmodium falciparum growth in vitro by impairment of choline transport. Antimicrob. Agents Chemother., 29, 814-820.
76. Ancelin, M.L., Vial, H.J., and Philippot, J.R. (1985) Inhibitors of choline transport into Plasmodium-infected erythrocytes are effective antiplasmodial compounds in vitro. Biochem. Pharmacol., 34, 4068-4071.
77. Choubey, V., Maity, P., Guha, M., Kumar, S., Srivastava, K., Puri, S.K., and Bandyopadhyay, U. (2007) Inhibition of Plasmodium falciparum choline kinase by hexadecyltrimethylammonium bromide: a possible antimalarial mechanism. Antimicrob. Agents Chemother., 51, 696-706.
78. Ancelin, M.L., Calas, M., Bompart, J., Cordina, G., Martin, D. et al. (1998) Antimalarial activity of 77 phospholipid polar head analogs: close correlation between inhibition of phospholipid metabolism and in vitro Plasmodium falciparum growth. Blood, 91, 1426-1437.
79. Ancelin, M.L., Calas, M., Bonhoure, A., Herbute, S., and Vial, H.J. (2003) In vivo antimalarial activities of mono-and bis quaternary ammonium salts interfering with Plasmodium phospholipid metabolism. Antimicrob. Agents Chemother., 47, 2598-2605.
80. Ancelin, M.L.,Calas, M., Vidal-Sailhan, V., Herbute, S., Ringwald, P., and Vial, H.J. (2003) Potent inhibitors of Plasmodium phospholipid metabolism with a broad spectrum of in vitro antimalarial activities. Antimicrob. Agents Chemother., 47, 2590-2597.
81. Calas, M., Ancelin, M.L., Cordina, G., Portefaix, P., Piquet, G., Vidal-Sailhan, V., and Vial, H. (2000) Antimalarial activity of compounds interfering with Plasmodium falciparum phospholipid metabolism: comparison between mono-and bisquaternary ammonium salts. J. Med. Chem., 43, 505-516.
82. Wengelnik, K., Vidal, V., Ancelin, M.L., Cathiard, A.M., Morgat, J.L. et al. (2002) A class of potent antimalarials and their specific accumulation in infected erythrocytes. Science, 295, 1311-1314.
83. Hamze, A., Rubi, E., Arnal, P., Boisbrun, M., Carcel, C. et al. (2005) Mono-and bis-thiazolium salts have potent antimalarial activity. J. Med. Chem., 48, 3639-3643.
84. Vial, H.J.,Wein, S., Farenc, C., Kocken, C., Nicolas, O. et al. (2004) Prodrugs of bisthiazolium salts are orally potent antimalarials. Proc. Natl Acad. Sci. USA, 101, 15458-15463.
85. Richier, E., Biagini, G.A., Wein, S., Boudou, F., Bray, P.G. et al. (2006) Potent antihematozoan activity of novel bisthiazolium drug T16: evidence for References j161inhibition of phosphatidylcholine metabolism in erythrocytes infected with Babesia and Plasmodium spp. Antimicrob. Agents Chemother., 50, 3381-3388.
86. Eastman, R.T. and Fidock, D.A. (2009) Artemisinin-based combination therapies: a vital tool in efforts to eliminate malaria. Nat. Rev. Microbiol., 7, 864-874.
87. Deves, R. and Krupka, R.M. (1979) The binding and translocation steps in transport as related to substrate structure. A study of the choline carrier of erythrocytes. Biochim. Biophys. Acta, 557, 469-485.
88. Roggero, R., Zufferey, R., Minca, M., Richier, E., Calas, M., Vial, H., and Ben Mamoun, C. (2004) Unraveling the mode of action of the antimalarial choline analog G25 in Plasmodium falciparum and Saccharomyces cerevisiae. Antimicrob. Agents Chemother., 48, 2816-2824.
89. Stead, A.M., Bray, P.G., Edwards, I.G., DeKoning, H.P., Elford, B.C., Stocks, P.A., and Ward, S.A. (2001) Diamidine compounds: selective uptake and targeting in Plasmodium falciparum. Mol. Pharmacol., 59, 1298-1306.
90. Ginsburg, H. and Stein, W.D. (2005) How many functional transport pathways does Plasmodium falciparum induce in the membrane of its host erythrocyte' Trends Parasitol., 21, 118-121.
91. Kirk, K. (2001)Membrane transport in the malaria-infected erythrocyte. Physiol. Rev., 81, 495-537.
92. Biagini, G.A., Richier, E., Bray, P.G.,Calas, M., Vial, H., and Ward, S.A. (2003) Heme binding contributes to antimalarial activity of bis-quaternary ammoniums. Antimicrob. Agents Chemother., 47, 2584-2589.
93. Vial, H.J., Eldin, P.,Martin, D., Gannoun, L., Calas, M., and Ancelin, M.L. (1999) Transport of phospholipid synthesis precursors and lipid trafficking into malaria-infected erythrocytes. Novartis Found. Symp., 226, 74-83; discussion 82-78.
94. Barrow, R.B. and Ing, H.R. (1948) Curare-like action of polymethylene bis-quaternary ammonium salts. Br. J. Pharmacol., 3, 298-304.
95. Roberts, E. (1992) The ligand binding site of the synaptosomal choline transporter: a provisional model based on inhibition studies. Neurochem. Res., 17, 509-528.
96. Surolia, A., Ramya, T., Ramya, V., and Surolia, N. (2004) FAS't inhibition of malaria. Biochem. J., 383 (3), 401-412.