Novel antimalarial drug targets: Hope for new antimalarial drugs

Expert Review of Clinical Pharmacology

Volumn 2, Issue 5, 2009, Pages 469-489

  Alam, Athar ^a   Goyal, Manish ^a   Iqbal, Mohd Shameel ^a   Pal, Chinmay ^a   Dey, Sumanta ^a   Bindu, Samik ^a   Maity, Pallab ^a   Bandyopadhyay, Uday ^a  

^a INDIAN INSTITUTE OF CHEMICAL BIOLOGY   (India)

Author keywords

Antimalarials; Apicoplast; Drug resistance; Drug target; Food vacuole; Malaria; Mitochondrion; Plasmodium falciparum; Target identification

Indexed keywords

ARTEMISININ DERIVATIVE; ATOVAQUONE; CHLOROQUINE; CHOLINE KINASE; CIPROFLOXACIN; CYCLIN DEPENDENT KINASE; DANTROLENE; DAPSONE; DOXYCYCLINE; ERYTHROCYTE MEMBRANE PROTEIN 1; FOSMIDOMYCIN; GELDANAMYCIN; GENOMIC DNA; HEMOGLOBIN; ISOPRENOID; LICOCHALCONE A; LONG CHAIN FATTY ACID COENZYME A LIGASE; MEMBRANE PHOSPHOLIPID; PROGUANIL; PURINE NUCLEOSIDE PHOSPHORYLASE; PYRIMETHAMINE; PYRUVATE KINASE; RAP1 PROTEIN; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; RIFAMPICIN; RITONAVIR; SAQUINAVIR; TETRACYCLINE; THIOLACTOMYCIN;

APICOPLAST; CELL CYCLE REGULATION; CELL VACUOLE; CLINICAL TRIAL; DNA METABOLISM; DRUG TARGETING; ENDOCYTOSIS; ERYTHROCYTE; FATTY ACID METABOLISM; GENE MUTATION; HEME SYNTHESIS; HUMAN; IC 50; MALARIA; MALARIA FALCIPARUM; MITOCHONDRION; OXIDATIVE STRESS; PLASMODIUM MALARIAE; POINT MUTATION; PROTEIN PROTEIN INTERACTION; PROTEOMICS; REVIEW; RNA INTERFERENCE; SIGNAL TRANSDUCTION; SPECIES INVASION; TRANSCRIPTION REGULATION;

EID: 70549098551     PISSN: 17512433     EISSN: None     Source Type: Journal    
DOI: 10.1586/ecp.09.28     Document Type: Review

References (238)

1. Sachs J, Malaney P. The economic and social burden of malaria. Nature 415(6872), 680-685 (2002).
2. Greenwood B, Mutabingwa T. Malaria in 2002. Nature 415(6872), 670-672 (2002).
3. Cowman AF, Crabb BS. Invasion of red blood cells by malaria parasites. Cell 124(4), 755-766 (2006). •• Describes the invasion pathway of the malaria parasite in detail, showing almost every important molecule involved in the parasite invasion of host cells. Targeting these molecule will block the parasite invasion and consequently the pathology to the host.
4. Allen RJ, Kirk K. Cell volume control in the Plasmodium-infected erythrocyte. Trends Parasitol. 20(1), 7-10 (2004). (Pubitemid 38045231)
5. Becker K, Tilley L, Vennerstrom JL, Roberts D, Rogerson S, Ginsburg H. Oxidative stress in malaria parasite-infected erythrocytes: host-parasite interactions. Int. J. Parasitol. 34(2), 163-189 (2004). (Pubitemid 38229822)
6. Choi SR, Mukherjee P, Avery MA. The fight against drug-resistant malaria: novel plasmodial targets and antimalarial drugs. Curr. Med. Chem. 15(2), 161-171 (2008). (Pubitemid 351234619)
7. Rosenthal P, Miller L. The need for new approaches to antimalarial chemotherapy. In: Antimalarial Chemotherapy. V. Georgiev (Ed.) Human Press Inc. Totowa NJ, USA 3-13 (2001). •• Discusses a very useful approach, called evolutionary patterning, to discover antimalarial drug targets with less chance of drug resistance owing to mutations of target molecules.
8. Durand PM, Naidoo K, Coetzer TL. Evolutionary patterning: a novel approach to the identification of potential drug target sites in Plasmodium falciparum. PLoS ONE 3(11), E3685 (2008).
9. Birkholtz L, van Brummelen AC, Clark K et al. Exploring functional genomics for drug target and therapeutics discovery in Plasmodia. Acta Trop. 105(2), 113-123 (2008).
10. Johnson P, Higgins AJ. Precise phenotypic anchoring for drug target identification, validation and biomarker discovery using an advanced system biology approach. Drug discovery world 55-62 (2004).
11. Jiang Z, Zhou Y. Using Gene networks to drug target identification. Journal of Integrative Bioinformatics 2(1), 14 (2005).
12. Wuchty S. Rich-club phenomenon in the interactome of P. falciparum - artifact or signature of a parasitic life style? PLoS ONE 2(3), E335 (2007).
13. Jana S, Paliwal J. Novel molecular targets for antimalarial chemotherapy. Int. J. Antimicrob. Agents 30(1), 4-10 (2007). (Pubitemid 46887588)
14. Price RN, Cassar C, Brockman A et al. The pfmdr1 gene is associated with a multidrug-resistant phenotype in Plasmodium falciparum from the western border of Thailand. Antimicrob. Agents Chemother. 43(12), 2943-2949 (1999).
15. Olliaro P. Mode of action and mechanisms of resistance for antimalarial drugs. Pharmacol. Ther. 89(2), 207-219 (2001). • Very good collection of contemporary knowledge on the mode of action and mechanism of resistance of drugs used against the malaria parasite. (Pubitemid 32333041)
16. Fidock DA, Nomura T, Talley AK et al. Mutations in the P. falciparum digestive vacuole transmembrane protein PfCRT and evidence for their role in chloroquine resistance. Mol. Cell. 6(4), 861-871 (2000).
17. Syafruddin D, Siregar JE, Marzuki S. Mutations in the cytochrome b gene of Plasmodium berghei conferring resistance to atovaquone. Mol. Biochem. Parasitol. 104(2), 185-194 (1999). (Pubitemid 29533306)
18. Plowe CV, Kublin JG, Doumbo OK. P. falciparum dihydrofolate reductase and dihydropteroate synthase mutations: epidemiology and role in clinical resistance to antifolates. Drug Resist. Updat. 1(6), 389-396 (1998).
19. Mugittu K, Genton B, Mshinda H, Beck HP. Molecular monitoring of Plasmodium falciparum resistance to artemisinin in Tanzania. Malar. J. 5, 126 (2006). (Pubitemid 46177993)
20. Stuart JM, Segal E, Koller D, Kim SK. A gene-coexpression network for global discovery of conserved genetic modules. Science 302(5643), 249-255 (2003). (Pubitemid 37248749)
21. Bergmann S, Ihmels J, Barkai N. Similarities and differences in genome-wide expression data of six organisms. PLoS Biol. 2(1), E9 (2004). (Pubitemid 39234589)
22. Chatr-aryamontri A, Ceol A, Palazzi LM et al. MINT: the molecular INTeraction database. Nucleic Acids Res. 35, D572-D574 (2007).
23. Striepen B, White MW, Li C et al. Genetic complementation in apicomplexan parasites. Proc. Natl Acad. Sci. USA 99(9), 6304-6309 (2002).
24. Reski R. Physcomitrella and Arabidopsis: the david and goliath of reverse genetics. Trends Plant Sci. 3, 209-210 (1998).
25. Schween G, Egener T, Fritzowsky D et al. Large-scale analysis of 73 329 physcomitrella plants transformed with different gene disruption libraries: production parameters and mutant phenotypes. Plant Biol. (Stuttg) 7(3), 228-237 (2005). (Pubitemid 40772315)
26. Li X, Chen H, Bahamontes-Rosa N et al. Plasmodium falciparum signal peptide peptidase is a promising drug target against blood stage malaria. Biochem. Biophys. Res. Commun. 380(3), 454-459 (2009).
27. Hodder AN, Drew DR, Epa VC et al. Enzymic, phylogenetic, and structural characterization of the unusual papainlike protease domain of Plasmodium falciparum SERA5. J. Biol. Chem. 278(48), 48169-48177 (2003).
28. Miller SK, Good RT, Drew DR et al. A subset of Plasmodium falciparum SERA genes are expressed and appear to play an important role in the erythrocytic cycle. J. Biol. Chem. 277(49), 47524-47532 (2002).
29. Salmon BL, Oksman A, Goldberg DE. Malaria parasite exit from the host erythrocyte: a two-step process requiring extraerythrocytic proteolysis. Proc. Natl Acad. Sci. USA 98(1), 271-276 (2001). (Pubitemid 32095899)
30. Glushakova S, Mazar J, Hohmann- Marriott MF, Hama E, Zimmerberg J. Irreversible effect of cysteine protease inhibitors on the release of malaria parasites from infected erythrocytes. Cell. Microbiol. 11(1), 95-105 (2009).
31. Arastu-Kapur S, Ponder EL, Fonovic UP et al. Identification of proteases that regulate erythrocyte rupture by the malaria parasite Plasmodium falciparum. Nat. Chem. Biol. 4(3), 203-213 (2008). (Pubitemid 351264129)
32. Yeoh S, O'Donnell RA, Koussis K et al. Subcellular discharge of a serine protease mediates release of invasive malaria parasites from host erythrocytes. Cell 131(6), 1072-1083 (2007). (Pubitemid 350235024)
33. Fairlie WD, Spurck TP, McCoubrie JE et al. Inhibition of malaria parasite development by a cyclic peptide that targets the vital parasite protein SERA5. Infect. Immun. 76(9), 4332-4344 (2008).
34. Goel VK, Li X, Chen H, Liu SC, Chishti AH, Oh SS. Band 3 is a host receptor binding merozoite surface protein 1 during the Plasmodium falciparum invasion of erythrocytes. Proc. Natl Acad. Sci. USA 100(9), 5164-5169 (2003). (Pubitemid 36542676)
35. O'Donnell RA, Saul A, Cowman AF, Crabb BS. Functional conservation of the malaria vaccine antigen MSP-119across distantly related Plasmodium species. Nat. Med. 6(1), 91-95 (2000). (Pubitemid 30048533)
36. Rayner JC, Vargas-Serrato E, Huber CS, Galinski MR, Barnwell JW. A Plasmodium falciparum homologue of Plasmodium vivax reticulocyte binding protein (PvRBP1) defines a trypsinresistant erythrocyte invasion pathway. J. Exp. Med. 194(11), 1571-1581 (2001). (Pubitemid 33126808)
37. Duraisingh MT, Triglia T, Ralph SA et al. Phenotypic variation of Plasmodium falciparum merozoite proteins directs receptor targeting for invasion of human erythrocytes. EMBO J. 22(5), 1047-1057 (2003). (Pubitemid 36313589)
38. Stubbs J, Simpson KM, Triglia T et al. Molecular mechanism for switching of P. falciparum invasion pathways into human erythrocytes. Science 309(5739), 1384-1387 (2005). (Pubitemid 41209367)
39. Triglia T, Duraisingh MT, Good RT, Cowman AF. Reticulocyte-binding protein homologue 1 is required for sialic acid-dependent invasion into human erythrocytes by Plasmodium falciparum. Mol. Microbiol. 55(1), 162-174 (2005). (Pubitemid 40127893)
40. Gaur D, Singh S, Jiang L, Diouf A, Miller LH. Recombinant Plasmodium falciparum reticulocyte homology protein 4 binds to erythrocytes and blocks invasion. Proc. Natl Acad. Sci. USA 104(45), 17789-17794 (2007). (Pubitemid 350210913)
41. Harnyuttanakorn P, McBride JS, Donachie S, Heidrich HG, Ridley RG. Inhibitory monoclonal antibodies recognise epitopes adjacent to a proteolytic cleavage site on the RAP-1 protein of Plasmodium falciparum. Mol. Biochem. Parasitol. 55(1-2), 177-186 (1992).
42. Howard RF, Jacobson KC, Rickel E, Thurman J. Analysis of inhibitory epitopes in the Plasmodium falciparum rhoptry protein RAP-1 including identification of a second inhibitory epitope. Infect. Immun. 66(1), 380-386 (1998). (Pubitemid 28018848)
43. Schofield L, Bushell GR, Cooper JA, Saul AJ, Upcroft JA, Kidson C. A rhoptry antigen of Plasmodium falciparum contains conserved and variable epitopes recognized by inhibitory monoclonal antibodies. Mol. Biochem. Parasitol. 18(2), 183-195 (1986). (Pubitemid 16159899)
44. Baldi DL, Andrews KT, Waller RF et al. RAP1 controls rhoptry targeting of RAP2 in the malaria parasite Plasmodium falciparum. EMBO J. 19(11), 2435-2443 (2000).
45. Crandall IE, Szarek WA, Vlahakis JZ et al. Sulfated cyclodextrins inhibit the entry of Plasmodium into red blood cells. Implications for malarial therapy. Biochem. Pharmacol. 73(5), 632-642 (2007).
46. Olliaro PL, Goldberg DE. The plasmodium digestive vacuole: metabolic headquarters and choice drug target. Parasitol. Today 11(8), 294-297 (1995).
47. Krugliak M, Zhang J, Ginsburg H. Intraerythrocytic Plasmodium falciparum utilizes only a fraction of the amino acids derived from the digestion of host cell cytosol for the biosynthesis of its proteins. Mol. Biochem. Parasitol. 119(2), 249-256 (2002). (Pubitemid 34114063)
48. Loria P, Miller S, Foley M, Tilley L. Inhibition of the peroxidative degradation of heme as the basis of action of chloroquine and other quinoline antimalarials. Biochem. J. 339(Pt 2), 363-370 (1999). (Pubitemid 29209967)
49. Dalal S, Klemba M. Roles for two aminopeptidases in vacuolar hemoglobin catabolizm in Plasmodium falciparum. J. Biol. Chem. 282(49), 35978-35987 (2007). • First report of two very important enzymes, aminopeptidases P and N, in the food vacuole to digest vacuolar hemoglobin, which could be potent antimalarial drug targets. (Pubitemid 350277126)
50. Lew VL, Tiffert T, Ginsburg H. Excess hemoglobin digestion and the osmotic stability of Plasmodium falciparum-infected red blood cells. Blood 101(10), 4189-4194 (2003). (Pubitemid 36857903)
51. Goldberg DE. Hemoglobin degradation. Curr. Top. Microbiol. Immunol. 295, 275-291 (2005).
52. Rosenthal PJ. Hydrolysis of erythrocyte proteins by proteases of malaria parasites. Curr. Opin. Hematol. 9(2), 140-145 (2002).
53. Klemba M, Gluzman I, Goldberg DE. A Plasmodium falciparum dipeptidyl aminopeptidase I participates in vacuolar hemoglobin degradation. J. Biol. Chem. 279(41), 43000-43007 (2004). (Pubitemid 39372193)
54. Dell'Agli M, Parapini S, Galli G et al. High antiplasmodial activity of novel plasmepsins I and II inhibitors. J. Med. Chem. 49(25), 7440-7449 (2006). (Pubitemid 44913403)
55. Dominguez JN, Leon C, Rodrigues J, Gamboa de Dominguez N, Gut J, Rosenthal PJ. Synthesis and evaluation of new antimalarial phenylurenyl chalcone derivatives. J. Med. Chem. 48(10), 3654-3658 (2005). (Pubitemid 40664115)
56. McGowan S, Porter CJ, Lowther J et al. Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase. Proc. Natl Acad. Sci. USA 106(8), 2537-2542 (2009).
57. Allary M, Schrevel J, Florent I. Properties, stage-dependent expression and localization of Plasmodium falciparum M1 family zinc-aminopeptidase. 125(Pt 1), 1-10 (2002).
58. Stack CM, Caffrey CR, Donnelly SM et al. Structural and functional relationships in the virulence-associated cathepsin L proteases of the parasitic liver fluke, Fasciola hepatica. J. Biol. Chem. 283(15), 9896-9908 (2008).
59. Skinner-Adams TS, Andrews KT, Melville L, McCarthy J, Gardiner DL. Synergistic interactions of the antiretroviral protease inhibitors saquinavir and ritonavir with chloroquine and mefloquine against Plasmodium falciparum in vitro. Antimicrob. Agents Chemother. 51(2), 759-762 (2007). (Pubitemid 46185303)
60. Kumar S, Guha M, Choubey V, Maity P, Bandyopadhyay U. Antimalarial drugs inhibiting hemozoin (β-hematin) formation: a mechanistic update. Life Sci. 80(9), 813-828 (2007). (Pubitemid 46149853)
61. Kumar S, Bandyopadhyay U. Free heme toxicity and its detoxification systems in human. Toxicol. Lett. 157(3), 175-188 (2005). (Pubitemid 40726102)
62. Goldberg DE, Slater AF. The pathway of hemoglobin degradation in malaria parasites. Parasitol. Today 8(8), 280-283 (1992).
63. Rathore D, Jani D, Nagarkatti R, Kumar S. Heme detoxification and antimalarial drugs - known mechanisms and future prospects. Drug Discov. Today Ther. Strateg. 3(2), 153-158 (2006). (Pubitemid 44173713)
64. Sullivan DJ Jr, Gluzman IY, Goldberg DE. Plasmodium hemozoin formation mediated by histidine-rich proteins. Science 271(5246), 219-222 (1996).
65. Dorn A, Stoffel R, Matile H, Bubendorf A, Ridley RG. Malarial haemozoin/β-haematin supports heme polymerization in the absence of protein. Nature 374(6519), 269-271 (1995).
66. Egan TJ, Ross DC, Adams PA. Quinoline anti-malarial drugs inhibit spontaneous formation of b-haematin (malaria pigment). FEBS Lett. 352(1), 54-57 (1994).
67. Bendrat K, Berger BJ, Cerami A. Haem polymerization in malaria. Nature 378(6553), 138-139 (1995).
68. Fitch CD. Ferriprotoporphyrin IX, phospholipids, and the antimalarial actions of quinoline drugs. Life Sci. 74(16), 1957-1972 (2004).
69. Fitch CD, Cai GZ, Chen YF, Shoemaker JD. Involvement of lipids in ferriprotoporphyrin IX polymerization in malaria. Biochim. Biophys. Acta. 1454(1), 31-37 (1999).
70. Jani D, Nagarkatti R, Beatty W et al. HDP-a novel heme detoxification protein from the malaria parasite. PLoS Pathog. 4(4), E1000053 (2008). (Pubitemid 351631069)
71. Kawazu S, Ikenoue N, Takemae H, Komaki-Yasuda K, Kano S. Roles of 1-Cys peroxiredoxin in heme detoxification in the human malaria parasite Plasmodium falciparum. FEBS J. 272(7), 1784-1791 (2005). (Pubitemid 40516227)
72. Wright CW, Addae-Kyereme J, Breen AG et al. Synthesis and evaluation of cryptolepine analogues for their potential as new antimalarial agents. J. Med. Chem. 44(19), 3187-3194 (2001). (Pubitemid 32862349)
73. Chou AC, Chevli R, Fitch CD. Ferriprotoporphyrin IX fulfills the criteria for identification as the chloroquine receptor of malaria parasites. Biochemistry 19(8), 1543-1549 (1980). (Pubitemid 10088203)
74. Kumar S, Das SK, Dey S et al. Antiplasmodial activity of [(aryl) arylsulfanylmethyl]Pyridine. Antimicrob. Agents Chemother. 52(2), 705-715 (2008).
75. Zoungrana A, Coulibaly B, Sie A et al. Safety and efficacy of methylene blue combined with artesunate or amodiaquine for uncomplicated falciparum malaria: a randomized controlled trial from Burkina Faso. PLoS ONE 3(2), e1630 (2008). (Pubitemid 351850988)
76. Desai SA. Targeting ion channels of Plasmodium falciparum-infected human erythrocytes for antimalarial development. Curr. Drug Targets Infect. Disord. 4(1), 79-86 (2004). •• Review describing the two unusual ion channels within the infected red blood cells complex, and presents novel opportunities for the identification of ion channel inhibitors that may be useful for the development of antimalarial compounds.
77. Desai SA, Bezrukov SM, Zimmerberg J. A voltage-dependent channel involved in nutrient uptake by red blood cells infected with the malaria parasite. Nature 406(6799), 1001-1005 (2000). (Pubitemid 30690466)
78. Desai SA, Krogstad DJ, McCleskey EW. A nutrient-permeable channel on the intraerythrocytic malaria parasite. Nature 362(6421), 643-646 (1993).
79. Saliba KJ, Kirk K. H+-coupled pantothenate transport in the intracellular malaria parasite. J. Biol. Chem. 276(21), 18115-18121 (2001). (Pubitemid 37411378)
80. Woodrow CJ, Penny JI, Krishna S. Intraerythrocytic Plasmodium falciparum expresses a high affinity facilitative hexose transporter. J. Biol. Chem. 274(11), 7272-7277 (1999). (Pubitemid 129505018)
81. Rager N, Mamoun CB, Carter NS, Goldberg DE, Ullman B. Localization of the Plasmodium falciparum PfNT1 nucleoside transporter to the parasite plasma membrane. J. Biol. Chem. 276(44), 41095-41099 (2001). (Pubitemid 37373264)
82. + in malaria-infected erythrocytes. Am. J. Physiol. Cell Physiol. 280(6), C1576-C1587 (2001).
83. Hill DA, Pillai AD, Nawaz F et al. A blasticidin S-resistant Plasmodium falciparum mutant with a defective plasmodial surface anion channel. Proc. Natl Acad. Sci. USA 104(3), 1063-1068 (2007). (Pubitemid 46154736)
84. Lisk G, Kang M, Cohn JV, Desai SA. Specific inhibition of the plasmodial surface anion channel by dantrolene. Eukaryot Cell 5(11), 1882-1893 (2006).
85. Ellekvist P, Maciel J, Mlambo G et al. Critical role of a K+ channel in Plasmodium berghei transmission revealed by targeted gene disruption. Proc. Natl Acad. Sci. USA 105(17), 6398-6402 (2008). (Pubitemid 351758357)
86. Joet T, Eckstein-Ludwig U, Morin C, Krishna S. Validation of the hexose transporter of Plasmodium falciparum as a novel drug target. Proc. Natl Acad. Sci. USA 100(13), 7476-7479 (2003). (Pubitemid 36759994)
87. Ouattara M, Wein S, Denoyelle S et al. Design and synthesis of amidoxime derivatives for orally potent C-alkylamidine-based antimalarial agents. Bioorg. Med. Chem. Lett. 19(3), 624-626 (2009).
88. Wengelnik K, Vidal V, Ancelin ML et al. A class of potent antimalarials and their specific accumulation in infected erythrocytes. Science 295(5558), 1311-1314 (2002). (Pubitemid 34157625)
89. Roggero R, Zufferey R, Minca M et al. Unraveling the mode of action of the antimalarial choline analog G25 in Plasmodium falciparum and Saccharomyces cerevisiae. Antimicrob. Agents Chemother. 48(8), 2816-2824 (2004). (Pubitemid 38989141)
90. Baldwin SA, McConkey GA, Cass CE, Young JD. Nucleoside transport as a potential target for chemotherapy in malaria. Curr. Pharm. Des. 13(6), 569-580 (2007).
91. Joet T, Morin C, Fischbarg J et al. Why is the Plasmodium falciparum hexose transporter a promising new drug target? Expert Opin. Ther. Targets 7(5), 593-602 (2003). (Pubitemid 37258838)
92. + antiport of Plasmodium falciparum membrane. J. Cell. Physiol. 154(3), 527-534 (1993).
93. Skinner-Adams T, Davis TM. Synergistic in vitro antimalarial activity of omeprazole and quinine. Antimicrob. Agents Chemother. 43(5), 1304-1306 (1999). (Pubitemid 29214771)
94. Skinner-Adams TS, Davis TM, Manning LS, Johnston WA. The efficacy of benzimidazole drugs against Plasmodium falciparum in vitro. Trans. R. Soc. Trop. Med. Hyg. 91(5), 580-584 (1997).
95. Nzila A, Mberu E, Bray P et al. Chemosensitization of Plasmodium falciparum by probenecid in vitro. Antimicrob. Agents Chemother. 47(7), 2108-2112 (2003). (Pubitemid 36753558)
96. Gero AM, O'Sullivan WJ. Purines and pyrimidines in malarial parasites. Blood Cells 16(2-3), 467-484, (1990).
97. Sherman IW. Biochemistry of Plasmodium (malarial parasites). Microbiol. Rev. 43(4), 453-495 (1979).
98. Hassan HF, Coombs GH. Purine and pyrimidine metabolism in parasitic protozoa. FEMS Microbiol. Rev. 4(1), 47-83 (1988).
99. Dawson PA, Cochran DA, Emmerson BT, Gordon RB. Inhibition of Plasmodium falciparum hypoxanthine-guanine phosphoribosyltransferase mRNA by antisense oligodeoxynucleotide sequence. Mol. Biochem. Parasitol. 60(1), 153-156 (1993).
100. Marshall VM, Coppel RL. Characterisation of the gene encoding adenylosuccinate lyase of Plasmodium falciparum. Mol. Biochem. Parasitol. 88(1-2), 237-241 (1997).
101. McConkey GA. Plasmodium falciparum: isolation and characterisation of a gene encoding protozoan GMP synthase. Exp. Parasitol. 94(1), 23-32 (2000).
102. Bhat JY, Shastri BG, Balaram H. Kinetic and biochemical characterization of Plasmodium falciparum GMP synthetase. Biochem. J. 409(1), 263-273 (2008).
103. Madrid DC, Ting LM, Waller KL, Schramm VL, Kim K. Plasmodium falciparum purine nucleoside phosphorylase is critical for viability of malaria parasites. J. Biol. Chem. 283(51), 35899-35907 (2008).
104. Olliaro PL, Yuthavong Y. An overview of chemotherapeutic targets for antimalarial drug discovery. Pharmacol. Ther. 81(2), 91-110 (1999). (Pubitemid 29073558)
105. Gero AM, Tetley K, Coombs GH, Phillips RS. Dihydroorotate dehydrogenase, orotate phosphoribosyltransferase and orotidine-5′- phosphate decarboxylase in Plasmodium falciparum. Trans. R. Soc. Trop. Med. Hyg. 75(5), 719-720 (1981).
106. Rathod PK, Reyes P. Orotidylatemetabolizing enzymes of the human malarial parasite, Plasmodium falciparum, differ from host cell enzymes. J. Biol. Chem. 258(5), 2852-2855 (1983).
107. Krungkrai J, Cerami A, Henderson GB. Pyrimidine biosynthesis in parasitic protozoa: purification of a monofunctional dihydroorotase from Plasmodium berghei and Crithidia fasciculata. Biochemistry 29(26), 6270-6275 (1990). (Pubitemid 20222245)
108. Krungkrai J. Purification, characterization and localization of mitochondrial dihydroorotate dehydrogenase in Plasmodium falciparum, human malaria parasite. Biochim. Biophys. Acta. 1243(3), 351-360 (1995).
109. Krungkrai J, Webster HK, Yuthavong Y. De novo and salvage biosynthesis of pteroylpentaglutamates in the human malaria parasite, Plasmodium falciparum. Mol. Biochem. Parasitol. 32(1), 25-37 (1989). (Pubitemid 18275862)
110. Asawamahasakda W, Yuthavong Y. The methionine synthesis cycle and salvage of methyltetrahydrofolate from host red cells in the malaria parasite (Plasmodium falciparum). Parasitology 107 (Pt 1), 1-10 (1993). (Pubitemid 23178170)
111. Ivanetich KM, Santi DV. Thymidylate synthase-dihydrofolate reductase in protozoa. Exp. Parasitol. 70(3), 367-371 (1990).
112. Carreras CW, Santi DV. The catalytic mechanism and structure of thymidylate synthase. Annu. Rev. Biochem. 64, 721-762 (1995).
113. Rathod PK, Leffers NP, Young RD. Molecular targets of 5-fluoroorotate in the human malaria parasite, Plasmodium falciparum. Antimicrob. Agents Chemother. 36(4), 704-711 (1992).
114. Medicines for Malaria Venture. Annual Report, 2007. Geneva, Switzerland(2007).
115. Tilley L, Loria P, Foley M. Chloroquine and other quinoline antimalarials. In: Antimalarial Chemotherapy. Totowa, Rosenthal PJ. (Ed.) Humana Press Totowa NJ, USA, 87-122 (2001).
116. Rahlfs S, Schirmer RH, Becker K. The thioredoxin system of Plasmodium falciparum and other parasites. Cell Mol. Life Sci. 59(6), 1024-1041 (2002). (Pubitemid 34734634)
117. Becker K, Rahlfs S, Nickel C, Schirmer RH. Glutathione - functions and metabolism in the malarial parasite Plasmodium falciparum. Biol. Chem. 384(4), 551-566 (2003). (Pubitemid 36609171)
118. Meierjohann S, Walter RD, Muller S. Glutathione synthetase from Plasmodium falciparum. Biochem. J. 363(Pt 3), 833-838 (2002).
119. Gilberger TW, Schirmer RH, Walter RD, Muller S. Deletion of the parasite-specific insertions and mutation of the catalytic triad in glutathione reductase from chloroquine-sensitive Plasmodium falciparum 3D7. Mol. Biochem. Parasitol. 107(2), 169-179 (2000). (Pubitemid 30213244)
120. Bruns CM, Hubatsch I, Ridderstrom M, Mannervik B, Tainer JA. Human glutathione transferase A4-4 crystal structures and mutagenesis reveal the basis of high catalytic efficiency with toxic lipid peroxidation products. J. Mol. Biol. 288(3), 427-439 (1999). (Pubitemid 29221812)
121. Rahlfs S, Nickel C, Deponte M, Schirmer RH, Becker K. Plasmodium falciparum thioredoxins and glutaredoxins as central players in redox metabolism. Redox Rep. 8(5), 246-250 (2003). (Pubitemid 38035581)
122. Flohe L, Hecht HJ, Steinert P. Glutathione and trypanothione in parasitic hydroperoxide metabolism. Free Radic. Biol. Med. 27(9-10), 966-984 (1999). (Pubitemid 29507470)
123. Kawazu S, Komaki K, Tsuji N et al. Molecular characterization of a 2-Cys peroxiredoxin from the human malaria parasite Plasmodium falciparum. Mol. Biochem. Parasitol. 116(1), 73-79 (2001). (Pubitemid 32706428)
124. Kawazu S, Tsuji N, Hatabu T, Kawai S, Matsumoto Y, Kano S. Molecular cloning and characterization of a peroxiredoxin from the human malaria parasite Plasmodium falciparum. Mol. Biochem. Parasitol. 109(2), 165-169 (2000). (Pubitemid 30665413)
125. Luersen K, Walter RD, Muller S. Plasmodium falciparum-infected red blood cells depend on a functional glutathione de novo synthesis attributable to an enhanced loss of glutathione. Biochem. J. 346 (Pt 2), 545-552 (2000). (Pubitemid 30148144)
126. Farber PM, Arscott LD, Williams CH Jr, Becker K, Schirmer RH. Recombinant Plasmodium falciparum glutathione reductase is inhibited by the antimalarial dye methylene blue. FEBS Lett. 422(3), 311-314 (1998). (Pubitemid 28075485)
127. Harwaldt P, Rahlfs S, Becker K. Glutathione S-transferase of the malarial parasite Plasmodium falciparum: characterization of a potential drug target. Biol. Chem. 383(5), 821-830 (2002). (Pubitemid 34649901)
128. Kumar S, Guha M, Choubey V et al. Bilirubin inhibits Plasmodium falciparum growth through the generation of reactive oxygen species. Free Radic. Biol. Med. 44(4), 602-613 (2008).
129. Trivedi V, Chand P, Srivastava K, Puri SK, Maulik PR, Bandyopadhyay U. Clotrimazole inhibits hemoperoxidase of Plasmodium falciparum and induces oxidative stress. Proposed antimalarial mechanism of clotrimazole. J. Biol. Chem. 280(50), 41129-41136 (2005). (Pubitemid 41832165)
130. Jefford CW. Why artemisinin and certain synthetic peroxides are potent antimalarials. Implications for the mode of action. Curr. Med. Chem. 8(15), 1803-1826 (2001).
131. Kamchonwongpaisan S, Meshnick SR. The mode of action of the antimalarial artemisinin and its derivatives. Gen. Pharmacol. 27(4), 587-592 (1996). (Pubitemid 26233325)
132. Jambou R, Legrand E, Niang M et al. Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6. Lancet 366(9501), 1960-1963 (2005).
133. Vennerstrom JL, Arbe-Barnes S, Brun R et al. Identification of an antimalarial synthetic trioxolane drug development candidate. Nature 430(7002), 900-904 (2004). (Pubitemid 39119218)
134. Aly NS, Hiramoto A, Sanai H et al. Proteome analysis of new antimalarial endoperoxide against Plasmodium falciparum. Parasitol. Res. 100(5), 1119-1124 (2007). (Pubitemid 46354890)
135. Le Roch KG, Johnson JR, Ahiboh H et al. 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 (2008).
136. Choubey V, Maity P, Guha M et al. Inhibition of Plasmodium falciparum choline kinase by hexadecyltrimethylammonium bromide: a possible antimalarial mechanism. Antimicrob. Agents Chemother. 51(2), 696-706 (2007). (Pubitemid 46185292)
137. Ancelin ML, Calas M, Bompart J et al. Antimalarial activity of 77 phospholipid polar head analogs: close correlation between inhibition of phospholipid metabolism and in vitro Plasmodium falciparum growth. Blood 91(4), 1426-1437 (1998). (Pubitemid 28086897)
138. Choubey V, Guha M, Maity P et al. Molecular characterization and localization of Plasmodium falciparum choline kinase. Biochim. Biophys. Acta. 1760(7), 1027-1038 (2006). (Pubitemid 43884961)
139. Calas M, Ancelin ML, Cordina G et al. Antimalarial activity of compounds interfering with Plasmodium falciparum phospholipid metabolism: comparison between mono- and bisquaternary ammonium salts. J. Med. Chem. 43(3), 505-516 (2000). (Pubitemid 30102090)
140. Calas M, Cordina G, Bompart J et al. Antimalarial activity of molecules interfering with Plasmodium falciparum phospholipid metabolism. Structure-activity relationship analysis. J. Med. Chem. 40(22), 3557-3566 (1997). (Pubitemid 27465088)
141. Ancelin ML, Calas M, Vidal-Sailhan V, Herbute S, Ringwald P, Vial HJ. Potent inhibitors of Plasmodium phospholipid metabolism with a broad spectrum of in vitro antimalarial activities. Antimicrob. Agents Chemother. 47(8), 2590-2597 (2003). (Pubitemid 36919464)
142. Ancelin ML, Calas M, Bonhoure A, Herbute S, Vial HJ. In vivo antimalarial activities of mono- and bis quaternary ammonium salts interfering with Plasmodium phospholipid metabolism. Antimicrob. Agents Chemother. 47(8), 2598-2605 (2003). (Pubitemid 36919465)
143. Vial HJ, Wein S, Farenc C et al. Prodrugs of bisthiazolium salts are orally potent antimalarials. Proc. Natl Acad. Sci. USA 101(43), 15458-15463 (2004). (Pubitemid 39441563)
144. Vance JE. Phospholipid synthesis in a membrane fraction associated with mitochondria. J. Biol. Chem. 265(13), 7248-7256 (1990).
145. Yeo HJ, Sri Widada J, Mercereau-Puijalon O, Vial HJ. Molecular cloning of CTP:phosphocholine cytidylyltransferase from Plasmodium falciparum. Eur. J. Biochem. 233(1), 62-72 (1995).
146. Arnot DE, Gull K. The Plasmodium cell-cycle: facts and questions. Ann. Trop. Med. Parasitol. 92(4), 361-365 (1998).
147. Waters NC, Geyer JA. Cyclin-dependent protein kinases as therapeutic drug targets for antimalarial drug development. Expert Opin. Ther. Targets 7(1), 7-17 (2003).
148. Doerig C, Chakrabarti D, Kappes B, Matthews K. The cell cycle in protozoan parasites. Prog. Cell. Cycle Res. 4, 163-183 (2000).
149. Graeser R, Wernli B, Franklin RM, Kappes B. Plasmodium falciparum protein kinase 5 and the malarial nuclear division cycles. Mol. Biochem. Parasitol. 82(1), 37-49 (1996). (Pubitemid 26376803)
150. Bracchi-Ricard V, Barik S, Delvecchio C, Doerig C, Chakrabarti R, Chakrabarti D. PfPK6, a novel cyclin-dependent kinase/ mitogen-activated protein kinase-related protein kinase from Plasmodium falciparum. Biochem. J. 347 (Pt 1), 255-263 (2000). (Pubitemid 30199065)
151. Geyer JA, Prigge ST, Waters NC. Targeting malaria with specific CDK inhibitors. Biochim. Biophys. Acta 1754(1-2), 160-170 (2005).
152. Waters NC, Woodard CL, Prigge ST. Cyclin H activation and drug susceptibility of the Pfmrk cyclin dependent protein kinase from Plasmodium falciparum. Mol. Biochem. Parasitol. 107(1), 45-55 (2000).
153. Shuttleworth J. The regulation and functions of cdk7. Prog. Cell. Cycle Res. 1, 229-240 (1995).
154. Geyer JA, Keenan SM, Woodard CL et al. Selective inhibition of Pfmrk, a Plasmodium falciparum CDK, by antimalarial 1,3-diaryl-2-propenones. Bioorg. Med. Chem. Lett. 19(7), 1982-1985 (2009).
155. Lang-Unnasch N. Purification and properties of Plasmodium falciparum malate dehydrogenase. Mol. Biochem. Parasitol. 50(1), 17-25 (1992).
156. Jacobasch G, Buckwitz D, Gerth C, Thamm R. Regulation of the energy metabolism of Plasmodium berghei. Biomed. Biochim. Acta 49(2-3), S289-294 (1990). (Pubitemid 20300794)
157. Mather MW, Vaidya AB. Mitochondria in malaria and related parasites: ancient, diverse and streamlined. J. Bioenerg. Biomembr. 40(5), 425-433 (2008).
158. Wilson RJ, Williamson DH. Extrachromosomal DNA in the Apicomplexa. Microbiol. Mol. Biol. Rev. 61(1), 1-16 (1997).
159. Feagin JE, Mericle BL, Werner E, Morris M. Identification of additional rRNA fragments encoded by the Plasmodium falciparum 6 kb element. Nucleic Acids Res. 25(2), 438-446 (1997). (Pubitemid 27303340)
160. van Dooren GG, Stimmler LM, McFadden GI. Metabolic maps and functions of the Plasmodium mitochondrion. FEMS Microbiol. Rev. 30(4), 596-630 (2006). •• Comparative study of existing biochemical and cell biological putative metabolic pathway of mitochondria with the available data from plasmodium falciparum genomic study.
161. Painter HJ, Morrisey JM, Mather MW, Vaidya AB. Specific role of mitochondrial electron transport in blood-stage Plasmodium falciparum. Nature 446(7131), 88-91 (2007).
162. Fujihashi M, Bello AM, Poduch E et al. An unprecedented twist to ODCase catalytic activity. J. Am. Chem. Soc. 127(43), 15048-15050 (2005). (Pubitemid 41547370)
163. Padmanaban G, Nagaraj VA, and, Rangarajan PN. Drugs and drug targets against malaria. Curr. Sci. 92(11), (2007).
164. Mather MW, Darrouzet E, Valkova-Valchanova M et al. Uncovering the molecular mode of action of the antimalarial drug atovaquone using a bacterial system. J. Biol. Chem. 280(29), 27458-27465 (2005). (Pubitemid 41040789)
165. Krungkrai J, Krungkrai SR, Suraveratum N, Prapunwattana P. Mitochondrial ubiquinol-cytochrome c reductase and cytochrome c oxidase: chemotherapeutic targets in malarial parasites. Biochem. Mol. Biol. Int. 42(5), 1007-1014 (1997). (Pubitemid 28297593)
166. Fry M, Pudney M. Site of action of the antimalarial hydroxynaphthoquinone, 2-[trans-4-(4′-chlorophenyl) cyclohexyl]-3- hydroxy-1,4-naphthoquinone (566C80). Biochem. Pharmacol. 43(7), 1545-1553 (1992).
167. Wilson RJ. Parasite plastids: approaching the endgame. Biol. Rev. Camb. Philos. Soc. 80(1), 129-153 (2005).
168. McFadden GI, Roos DS. Apicomplexan plastids as drug targets. Trends Microbiol. 7(8), 328-333 (1999).
169. Ralph SA, D'Ombrain MC, McFadden GI. The apicoplast as an antimalarial drug target. Drug Resist. Updat. 4(3), 145-151 (2001).
170. Lee PJ, Bhonsle JB, Gaona HW et al. Targeting the Fatty Acid Biosynthesis Enzyme, b-Ketoacyl-Acyl Carrier Protein Synthase III (PfKASIII), in the Identification of Novel Antimalarial Agents. J. Med. Chem. 52(4), 952-963 (2009).
171. Lu JZ, Lee PJ, Waters NC, Prigge ST. Fatty acid synthesis as a target for antimalarial drug discovery. Comb. Chem. High. Throughput Screen 8(1), 15-26 (2005).
172. Prigge ST, He X, Gerena L, Waters NC, Reynolds KA. The initiating steps of a type II fatty acid synthase in Plasmodium falciparum are catalyzed by pfACP, pfMCAT, and pfKASIII. Biochemistry 42(4), 1160-1169 (2003). (Pubitemid 36159551)
173. He X, Reeve AM, Desai UR, Kellogg GE, Reynolds KA. 1,2-dithiole-3-ones as potent inhibitors of the bacterial 3-ketoacyl acyl carrier protein synthase III (FabH). Antimicrob. Agents Chemother. 48(8), 3093-3102 (2004). (Pubitemid 38989179)
174. Vaughan AM, O'Neill MT, Tarun AS et al. Type II fatty acid synthesis is essential only for malaria parasite late liver stage development. Cell. Microbiol. 11(3), 506-520 (2009).
175. Karioti A, Skaltsa H, Zhang X et al. Inhibiting enoyl-ACP reductase (FabI) across pathogenic microorganisms by linear sesquiterpene lactones from Anthemis auriculata. Phytomedicine 15(12), 1125-1129 (2008).
176. Surolia N, Surolia A. Triclosan offers protection against blood stages of malaria by inhibiting enoyl-ACP reductase of Plasmodium falciparum. Nat. Med. 7(2), 167-173 (2001). (Pubitemid 32148482)
177. Kuntz L, Tritsch D, Grosdemange-Billiard C et al. Isoprenoid biosynthesis as a target for antibacterial and antiparasitic drugs: phosphonohydroxamic acids as inhibitors of deoxyxylulose phosphate reductoisomerase. Biochem. J. 386(Pt 1), 127-135 (2005). (Pubitemid 40289232)
178. Nallan L, Bauer KD, Bendale P et al. Protein farnesyltransferase inhibitors exhibit potent antimalarial activity. J. Med. Chem. 48(11), 3704-3713 (2005). (Pubitemid 40776846)
179. Sato S, Clough B, Coates L, Wilson RJ. Enzymes for heme biosynthesis are found in both the mitochondrion and plastid of the malaria parasite Plasmodium falciparum. Protist 155(1), 117-125 (2004). (Pubitemid 38503630)
180. Ralph SA, van Dooren GG, Waller RF et al. Tropical infectious diseases: metabolic maps and functions of the Plasmodium falciparum apicoplast. Nat. Rev. Microbiol. 2(3), 203-216 (2004).
181. Bonday ZQ, Taketani S, Gupta PD, Padmanaban G. Heme biosynthesis by the malarial parasite. Import of deltaaminolevulinate dehydrase from the host red cell. J. Biol. Chem. 272(35), 21839-21846 (1997). (Pubitemid 27382800)
182. Varadharajan S, Sagar BK, Rangarajan PN, Padmanaban G. Localization of ferrochelatase in Plasmodium falciparum. Biochem. J. 384(Pt 2), 429-436 (2004).
183. Dhanasekaran S, Chandra NR, Chandrasekhar Sagar BK, Rangarajan PN, Padmanaban G. d-aminolevulinic acid dehydratase from Plasmodium falciparum: indigenous versus imported. J. Biol. Chem. 279(8), 6934-6942 (2004). (Pubitemid 38248836)
184. Varadharajan S, Dhanasekaran S, Bonday ZQ, Rangarajan PN, Padmanaban G. Involvement of d-aminolaevulinate synthase encoded by the parasite gene in de novo heme synthesis by Plasmodium falciparum. Biochem. J. 367(Pt 2), 321-327 (2002). (Pubitemid 35216806)
185. Padmanaban G, Nagaraj VA, Rangarajan PN. An alternative model for heme biosynthesis in the malarial parasite. Trends Biochem. Sci. 32(10), 443-449 (2007). (Pubitemid 47588947)
186. Wiesner J, Jomaa H. Isoprenoid biosynthesis of the apicoplast as drug target. Curr. Drug Targets 8(1), 3-13 (2007). (Pubitemid 46043895)
187. Pink R, Hudson A, Mouries MA, Bendig M. Opportunities and challenges in antiparasitic drug discovery. Nat. Rev. Drug Discov. 4(9), 727-740 (2005). (Pubitemid 43090494)
188. Krishna S. Drug development papers in PLoS Medicine: how we try to spot a winner. PLoS Med. 3(12), E547 (2006).
189. Carraz M, Jossang A, Franetich JF et al. A plant-derived morphinan as a novel lead compound active against malaria liver stages. PLoS Med. 3(12), E513 (2006).
190. Oleinikov AV, Amos E, Frye IT et al. High throughput functional assays of the variant antigen PfEMP1 reveal a single domain in the 3D7 Plasmodium falciparum genome that binds ICAM1 with high affinity and is targeted by naturally acquired neutralizing antibodies. PLoS Pathog. 5(4), E1000386 (2009).
191. Vogt AM, Pettersson F, Moll K et al. Release of sequestered malaria parasites upon injection of a glycosaminoglycan. PLoS Pathog. 2(9), E100 (2006).
192. Yearick K, Ekoue-Kovi K, Iwaniuk DP et al. Overcoming drug resistance to heme-targeted antimalarials by systematic side chain variation of 7-chloro-4- aminoquinolines. J. Med. Chem. 51(7), 1995-1998 (2008).
193. Sunduru N, Srivastava K, Rajakumar S, Puri SK, Saxena JK, Chauhan PM. Synthesis of novel thiourea, thiazolidinedione and thioparabanic acid derivatives of 4-aminoquinoline as potent antimalarials. Bioorg. Med. Chem. Lett. 19(9), 2570-2573 (2009).
194. Krishna S, Woodrow CJ, Staines HM, Haynes RK, Mercereau-Puijalon O. Re-evaluation of how artemisinins work in light of emerging evidence of in vitro resistance. Trends Mol. Med. 12(5), 200-205 (2006). (Pubitemid 43728412)
195. Harris KS, Casey JL, Coley AM et al. Rapid optimization of a peptide inhibitor of malaria parasite invasion by comprehensive N-methyl scanning. J. Biol. Chem. 284(14), 9361-9371 (2009).
196. Nezami A, Luque I, Kimura T, Kiso Y, Freire E. Identification and characterization of allophenylnorstatinebased inhibitors of plasmepsin II, an antimalarial target. Biochemistry 41(7), 2273-2280 (2002). (Pubitemid 34160888)
197. De D, Krogstad FM, Byers LD, Krogstad DJ. Structure-activity relationships for antiplasmodial activity among 7-substituted 4-aminoquinolines. J. Med. Chem. 41(25), 4918-4926 (1998).
198. Stocks PA, Raynes KJ, Bray PG, Park BK, O'Neill PM, Ward SA. Novel short chain chloroquine analogues retain activity against chloroquine resistant K1 Plasmodium falciparum. J. Med. Chem. 45(23), 4975-4983 (2002).
199. Saliba KJ, Kirk K. pH regulation in the intracellular malaria parasite, Plasmodium falciparum. H(+) extrusion via a v-type h(+)-atpase. J. Biol. Chem. 274(47), 33213-33219 (1999).
200. Kirk K. Channels and transporters as drug targets in the Plasmodium-infected erythrocyte. Acta Trop. 89(3), 285-298 (2004). (Pubitemid 38117065)
201. Tuteja R. Helicases - feasible antimalarial drug target for Plasmodium falciparum. FEBS J. 274(18), 4699-4704 (2007). (Pubitemid 47353124)
202. Dow GS, Chen Y, Andrews KT et al. Antimalarial activity of phenylthiazolylbearing hydroxamate-based histone deacetylase inhibitors. Antimicrob. Agents Chemother. 52(10), 3467-3477 (2008).
203. Mukherjee P, Pradhan A, Shah F, Tekwani BL, Avery MA. Structural insights into the Plasmodium falciparum histone deacetylase 1 (PfHDAC-1): A novel target for the development of antimalarial therapy. Bioorg. Med. Chem. 16(9), 5254-5265 (2008). (Pubitemid 351625863)
204. Yanow SK, Purcell LA, Lee M, Spithill TW. Genomics-based drug design targets the AT-rich malaria parasite: implications for antiparasite chemotherapy. Pharmacogenomics 8(9), 1267-1272 (2007). (Pubitemid 47578233)
205. Yanow SK, Purcell LA, Pradel G et al. Potent antimalarial and transmissionblocking activities of centanamycin, a novel DNA-binding agent. J. Infect. Dis. 197(4), 527-534 (2008). (Pubitemid 351321529)
206. Cui L, Miao J. Cytotoxic effect of curcumin on malaria parasite Plasmodium falciparum: inhibition of histone acetylation and generation of reactive oxygen species. Antimicrob. Agents Chemother. 51(2), 488-494 (2007). (Pubitemid 46185265)
207. Razakantoanina V, Nguyen Kim PP, Jaureguiberry G. Antimalarial activity of new gossypol derivatives. Parasitol. Res. 86(8), 665-668 (2000). (Pubitemid 30707765)
208. Banumathy G, Singh V, Pavithra SR, Tatu U. Heat shock protein 90 function is essential for Plasmodium falciparum growth in human erythrocytes. J. Biol. Chem. 278(20), 18336-18345 (2003). (Pubitemid 36799454)
209. Woodard CL, Li Z, Kathcart AK et al. Oxindole-based compounds are selective inhibitors of Plasmodium falciparum cyclin dependent protein kinases. J. Med. Chem. 46(18), 3877-3882 (2003). (Pubitemid 37034137)
210. Harrison T, Samuel BU, Akompong T et al. Erythrocyte G protein-coupled receptor signaling in malarial infection. Science 301(5640), 1734-1736 (2003). (Pubitemid 37174369)
211. Murphy SC, Harrison T, Hamm HE, Lomasney JW, Mohandas N, Haldar K. Erythrocyte G protein as a novel target for malarial chemotherapy. PLoS Med. 3(12), e528 (2006).
212. Reungprapavut S, Krungkrai SR, Krungkrai J. Plasmodium falciparum carbonic anhydrase is a possible target for malaria chemotherapy. J. Enzyme Inhib. Med. Chem. 19(3), 249-256 (2004). (Pubitemid 39004278)
213. Krauth-Siegel RL, Coombs GH. Enzymes of parasite thiol metabolism as drug targets. Parasitol. Today 15(10), 404-409 (1999).
214. Eckstein-Ludwig U, Webb RJ, Van Goethem ID et al. Artemisinins target the SERCA of Plasmodium falciparum. Nature 424(6951), 957-961 (2003). (Pubitemid 37051688)
215. Chatterjee M, Chatterjee N, Datta R, Datta B, Gupta NK. Expression and activity of p67 are induced during heat shock. Biochem. Biophys. Res. Commun. 249(1), 113-117 (1998). (Pubitemid 28418704)
216. Chen X, Chong CR, Shi L, Yoshimoto T, Sullivan DJ Jr, Liu JO. Inhibitors of Plasmodium falciparum methionine aminopeptidase 1b possess antimalarial activity. Proc. Natl Acad. Sci. USA 103(39), 14548-14553 (2006). (Pubitemid 44484787)
217. Muller IB, Das Gupta R, Luersen K, Wrenger C, Walter RD. Assessing the polyamine metabolism of Plasmodium falciparum as chemotherapeutic target. Mol. Biochem. Parasitol. 160(1), 1-7 (2008). (Pubitemid 351694359)
218. Nakanishi M. S-adenosyl-L-homocysteine hydrolase as an attractive target for antimicrobial drugs. Yakugaku Zasshi 127(6), 977-982 (2007). (Pubitemid 46855539)
219. Jiang L, Lee PC, White J, Rathod PK. Potent and selective activity of a combination of thymidine and 1843U89, a folate-based thymidylate synthase inhibitor, against Plasmodium falciparum. Antimicrob. Agents Chemother. 44(4), 1047-1050 (2000). (Pubitemid 30165289)
220. Spry C, Kirk K, Saliba KJ. Coenzyme A biosynthesis: an antimicrobial drug target. FEMS Microbiol. Rev. 32(1), 56-106 (2008). (Pubitemid 350293916)
221. Mi-Ichi F, Miyadera H, Kobayashi T et al. Parasite mitochondria as a target of chemotherapy: inhibitory effect of licochalcone A on the Plasmodium falciparum respiratory chain. Ann. NY Acad. Sci. 1056, 46-54 (2005). (Pubitemid 43030966)
222. Biagini GA, Viriyavejakul P, O'Neill PM, Bray PG, Ward SA. Functional characterization and target validation of alternative complex I of Plasmodium falciparum mitochondria. Antimicrob. Agents Chemother. 50(5), 1841-1851 (2006).
223. Gujjar R, Marwaha A, El Mazouni F et al. Identification of a metabolically stable triazolopyrimidine-based dihydroorotate dehydrogenase inhibitor with antimalarial activity in mice. J. Med. Chem. 52(7), 1864-1872 (2009).
224. Yuvaniyama J, Chitnumsub P, Kamchonwongpaisan S et al. Insights into antifolate resistance from malarial DHFR-TS structures. Nat. Struct. Biol. 10(5), 357-365 (2003). (Pubitemid 36523270)
225. Triglia T, Menting JG, Wilson C, Cowman AF. Mutations in dihydropteroate synthase are responsible for sulfone and sulfonamide resistance in Plasmodium falciparum. Proc. Natl Acad. Sci. USA 94(25), 13944-13949 (1997). (Pubitemid 28009689)
226. Budimulja AS, Syafruddin, Tapchaisri P, Wilairat P, Marzuki S. The sensitivity of Plasmodium protein synthesis to prokaryotic ribosomal inhibitors. Mol. Biochem. Parasitol. 84(1), 137-141 (1997). (Pubitemid 27090514)
227. Clough B, Rangachari K, Strath M, Preiser PR, Wilson RJ. Antibiotic inhibitors of organellar protein synthesis in Plasmodium falciparum. Protist 150(2), 189-195 (1999). (Pubitemid 29442459)
228. Pukrittayakamee S, Viravan C, Charoenlarp P, Yeamput C, Wilson RJ, White NJ. Antimalarial effects of rifampin in Plasmodium vivax malaria. Antimicrob. Agents Chemother. 38(3), 511-514 (1994). (Pubitemid 24072240)
229. Meinnel T. Peptide deformylase of eukaryotic protists: a target for new antiparasitic agents? Parasitol. Today 16(4), 165-168 (2000). (Pubitemid 30163003)
230. Weissig V, Vetro-Widenhouse TS, Rowe TC. Topoisomerase II inhibitors induce cleavage of nuclear and 35-kb plastid DNAs in the malarial parasite Plasmodium falciparum. DNA Cell. Biol. 16(12), 1483-1492 (1997). (Pubitemid 28070528)
231. Divo AA, Sartorelli AC, Patton CL, Bia FJ. Activity of fluoroquinolone antibiotics against Plasmodium falciparum in vitro. Antimicrob. Agents Chemother. 32(8), 1182-1186 (1988).
232. Waller RF, Keeling PJ, Donald RG et al. Nuclear-encoded proteins target to the plastid in Toxoplasma gondii and Plasmodium falciparum. Proc. Natl Acad. Sci. USA 95(21), 12352-12357 (1998).
233. Jomaa H, Wiesner J, Sanderbrand S et al. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Science 285(5433), 1573-1576 (1999). (Pubitemid 29420582)
234. Ohkanda J, Lockman JW, Yokoyama K et al. Peptidomimetic inhibitors of protein farnesyltransferase show potent antimalarial activity. Bioorg. Med. Chem. Lett. 11(6), 761-764 (2001). (Pubitemid 32230674)
235. Fitzpatrick T, Ricken S, Lanzer M, Amrhein N, Macheroux P, Kappes B. Subcellular localization and characterization of chorismate synthase in the apicomplexan Plasmodium falciparum. Mol. Microbiol. 40(1), 65-75 (2001). (Pubitemid 32322862)
236. Keeling PJ, Palmer JD, Donald RG, Roos DS, Waller RF, McFadden GI. Shikimate pathway in apicomplexan parasites. Nature 397(6716), 219-220 (1999).
237. MINT http://mint.bio.uniroma2.it/mint/
238. Genome sequence of Plasmodium www.plasmodb.org