Table 2.

Antimalarial compounds active against old and new targets

Examples
Target locationPathway/mechanismTarget moleculeExisting therapiesNew compoundsReferences (new agents)
Cytosol Folate metabolism Dihydrofolate reductase Pyrimethamine, proguanil Chorproguanil Nzila et al., 2000; Mutabingwa et al., 2001 
  Dihydropteroate synthase Sulfadoxine, dapsone   
  Thymidylate synthase  5-fluoroorotate Rathod et al., 1992 
 Glycolysis Lactate dehydrogenase  Gossypol derivatives Razakantoanina et al., 2000 
      
Parasite membrane Phospholipid synthesis Choline transporter  G25 Wengelnik et al., 2002 
 Membrane transport Unique channels  Dinucleoside dimers Gero et al., 2003 
      
Food vacuole Heme polymerization Hemozoin Quinolines New quinolines De et al., 1998; Stocks et al., 2002 
 Hemoglobin hydrolysis Plasmepsins  Protease inhibitors Francis et al., 1994; Haque et al., 1999 
  Falcipains  Protease inhibitors Rosenthal, 2001b; Shenai et al., 2003 
 Free radical generation Unknown Artemisinins New peroxides Vennerstrom et al., 2000; Borstnik et al., 2002 
      
Mitochondrion Electron transport Cyt. c oxidoreductase Atovaquone   
      
Apicoplast Protein synthesis Apicoplast ribosome Antibiotics   
 DNA synthesis DNA gyrase Quinolones   
 Transcription RNA polymerase Rifampin   
 Type II fatty acid biosynthesis FabH  Thiolactomycin Waller et al., 1998 
  FabI  Triclosan Surolia and Surolia, 2001 
 Isoprenoid synthesis DOXP reductoisomerase  Fosmidomycin Jomaa et al., 1999 
 Protein farnesylation Farnesyl transferase  Peptidomimetics Ohkanda et al., 2001; Chakrabarti et al., 2002 
Examples
Target locationPathway/mechanismTarget moleculeExisting therapiesNew compoundsReferences (new agents)
Cytosol Folate metabolism Dihydrofolate reductase Pyrimethamine, proguanil Chorproguanil Nzila et al., 2000; Mutabingwa et al., 2001 
  Dihydropteroate synthase Sulfadoxine, dapsone   
  Thymidylate synthase  5-fluoroorotate Rathod et al., 1992 
 Glycolysis Lactate dehydrogenase  Gossypol derivatives Razakantoanina et al., 2000 
      
Parasite membrane Phospholipid synthesis Choline transporter  G25 Wengelnik et al., 2002 
 Membrane transport Unique channels  Dinucleoside dimers Gero et al., 2003 
      
Food vacuole Heme polymerization Hemozoin Quinolines New quinolines De et al., 1998; Stocks et al., 2002 
 Hemoglobin hydrolysis Plasmepsins  Protease inhibitors Francis et al., 1994; Haque et al., 1999 
  Falcipains  Protease inhibitors Rosenthal, 2001b; Shenai et al., 2003 
 Free radical generation Unknown Artemisinins New peroxides Vennerstrom et al., 2000; Borstnik et al., 2002 
      
Mitochondrion Electron transport Cyt. c oxidoreductase Atovaquone   
      
Apicoplast Protein synthesis Apicoplast ribosome Antibiotics   
 DNA synthesis DNA gyrase Quinolones   
 Transcription RNA polymerase Rifampin   
 Type II fatty acid biosynthesis FabH  Thiolactomycin Waller et al., 1998 
  FabI  Triclosan Surolia and Surolia, 2001 
 Isoprenoid synthesis DOXP reductoisomerase  Fosmidomycin Jomaa et al., 1999 
 Protein farnesylation Farnesyl transferase  Peptidomimetics Ohkanda et al., 2001; Chakrabarti et al., 2002 
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