94
Views
5
CrossRef citations to date
0
Altmetric
Review

Dihydrofolate reductase inhibitors: developments in antiparasitic chemotherapy

, , &
Pages 143-157 | Published online: 22 Feb 2008

Bibliography

  • Greenwood B, Mutabingwa T. Malaria in 2002. Nature 2002;415:670-2
  • Sachs J, Malaney P. The economic and social burden of malaria. Nature 2002;415:680-5
  • Hyde J. Exploring the folate pathway in Plasmodium falciparum. Acta Tropica 2005;94:191-206
  • Nzila A. The past, present and future of antifolates in the treatment of Plasmodium falciparum infection. J Antimicrob Chemother 2006;57:1043-54
  • Gangjee A, Yu J, Copper JE, Smith CD. Discovery of novel antitumor antimitotic agents that also reverse tumor resistance. J Med Chem 2007;50(14):3290-301
  • Klepser M, Klepser T. Drug treatment of HIV-related opportunistic infections. Drugs 1997;53:40-73
  • Aspinall T, Joynson D, Guy E, et al. The molecular basis of sulfonamide resistance in Toxoplasma gondii and implications for the clinical management of toxoplasmosis. J Infect Dis 2002;185:1637-43
  • Gregson A, Plowe C. Mechanisms of resistance of malaria parasites to antifolates. Pharmacol Rev 2005;57:117-45
  • Looareesuwan S, Harinasuta T, Chongsuphajaisiddhi T. Drug resistant malaria, with special reference to Thailand. Southeast Asian J Trop Med Public Health 1992;23:621-34
  • Wang P, Lee C, Bayoumi R, et al. Resistance to antifolates in Plasmodium falciparum monitored by sequence analysis of dihydropteroate synthase and dihydrofolate reductase alleles in a large number of field samples of diverse origins. Mol Biochem Parasitol 1997;89:161-77
  • Sirawaraporn W, Sathitkul T, Sirawaraporn R, et al. Antifolate-resistant mutants of Plasmodium falciparum dihydrofolate reductase. Proc Natl Acad Sci USA 1997;94:1124-9
  • Yuvaniyama J, Chitnumsub P, Kamchonwongpaisan S, et al. Insights into antifolate resistance from malarial DHFR-TS structures. Nat Struct Biol 2003;10:357-65
  • Canfield C, Milhous W, Ager A, et al. PS-15: a potent, orally active antimalarial from a new class of folic acid antagonists. Am J Trop Med Hyg 1993;49:121-6
  • Rieckmann K, Yeo A, Edstein M. Activity of PS-15 and its metabolite, WR99210, against Plasmodium falciparum in an in vivo-in vitro model. Trans R Soc Trop Med Hyg 1996;90:568-71
  • Jensen N, Ager A, Bliss R, et al. Phenoxypropoxybiguanides, prodrugs of DHFR-inhibiting diaminotriazine antimalarials. J Med Chem 2001;44:3925-31
  • Alloueche A, Bailey W, Barton S, et al. Comparison of chlorproguanil-dapsone with sulfadoxine-pyrimethamine for the treatment of uncomplicated falciparum malaria in young African children: double-blind randomised controlled trial. Lancet 2004;363:1843-8
  • Anderson A. Two crystal structures of dihydrofolate reductase-thymidylate synthase from cryptosporidium hominis reveal protein:ligand interactions including a structural basis for observed antifolate resistance. Acta Cryst 2005;F61:258-62
  • O'Neil R, Lilien R, Donald B, et al. Phylogenetic classification of protozoa based on the structure of the linker domain in the bifunctional enzyme, dihydrofolate reductase-thymidylate synthase. J Biol Chem 2003;278:52980-7
  • O'Neil R, Lilien R, Donald B, et al. The crystal structure of dihydrofolate reductase-thymidylate synthase from cryptosporidium hominis reveals a novel architecture for the bifunctional enzyme. J Eukaryot Microbiol 2003;50 Suppl:555-6
  • Pelphrey P, Popov V, Joska T, et al. Highly efficient ligands for DHFR from Cryptosporidium hominis and Toxoplasma gondii inspired by structural analysis. J Med Chem 2007;50:940-50
  • Knighton D, Kan C, Howland E, et al. Structure of and kinetic channeling in bifunctional dihydrofolate reductase-thymidylate synthase. Nat Struct Biol 1994;1:186-94
  • Dana Farber Cancer Institute. US7119095 (2006)
  • Dana Farber Cancer Institute. US7056911 (2006)
  • Rosowsky & Forsch. US20060142315 (2006)
  • Rosowsky A, Forsch RA, Queener SF. Inhibition of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium avium dihydrofolate reductases by 2,4-diamino-5-[2-methoxy-5-(omega-carboxyalkyloxy)benzyl]pyrimidines: marked improvement in potency relative to trimethoprim and species selectivity relative to piritrexim. J Med Chem 2002;45(1):233-41
  • Rosowsky A, Forsch RA, Queener SF. Further studies on 2,4-diamino-5-(2′,5′-disubstituted benzyl)pyrimidines as potent and selective inhibitors of dihydrofolate reductases from three major opportunistic pathogens of AIDS. J Med Chem 2003;46(9):1726-36
  • Dana Farber Cancer Institute. WO2004082613; 2004
  • Chan DC, Laughton CA, Queener SF, Stevens MF. Structural studies on bioactive compounds. 34. Design, synthesis, and biological evaluation of triazenyl-substituted pyrimethamine inhibitors of Pneumocystis carinii dihydrofolate reductase. J Med Chem 2001;44(16):2555-64
  • British Technology Group Ltd. US5618928; 1997
  • Stevens MF, Phillip KS, Rathbone DL, et al. Structural studies on bioactive compounds. 28. Selective activity of triazenyl-substituted pyrimethamine derivatives against Pneumocystis carinii dihydrofolate reductase. J Med Chem 1997;40(12):1886-93
  • Tarnchompoo B, Sirichaiwat C, Phupong W, et al. Development of 2,4-diaminopyrimidines as antimalarials based on inhibition of the S108N and C59R+S108N mutants of dihydrofolate reductase from pyrimethamine-resistant Plasmodium falciparum. J Med Chem 2002;45(6):1244-52
  • Kamchonwongpaisan S, Quarrell R, Chareonsethakul N, et al. Inhibitors of multiple mutants of Plasmodium falciparum dihydrofolate reductase and their antimalarial activities. J Med Chem 2004;47:673-80
  • National Science and Technology Development Agency. US20040180913; 2004
  • Kamchonwongpaisan S, Quarrell R, Charoensetakul N, et al. Inhibitors of multiple mutants of Plasmodium falciparum dihydrofolate reductase and their antimalarial activities. J Med Chem 2004;47(3):673-80
  • Yuthavong Y, Vilaivan T, Chareonsethakul N, et al. Development of a lead inhibitor for the A16V+S108T mutant of dihydrofolate reductase from the cycloguanil-resistant strain (T9/94) of Plasmodium falciparum. J Med Chem 2000;43(14):2738-44
  • Lowe. WO2001053276 (2001)
  • Jacobus Pharmaceutical Co., Inc. US6551614 (2003)
  • Jacobus Pharmaceutical Co., Inc. US6693217; 2004
  • Jacobus Pharmaceutical Co., Inc. US7256218 (2007)
  • Glaxo Wellcome, Inc. US6166046 (2000)
  • Smithkline Beecham Corp. US6413993 (2002)
  • Chan DC, Fu H, Forsch RA, et al. Design, synthesis, and antifolate activity of new analogues of piritrexim and other diaminopyrimidine dihydrofolate reductase inhibitors with omega-carboxyalkoxy or omega-carboxy-1-alkynyl substitution in the side chain. J Med Chem 2005;48(13):4420-31
  • Dana Farber Cancer Institute. US7256197 (2007)
  • Rosowsky A, Cody V, Galitsky N, et al. Structure-based design of selective inhibitors of dihydrofolate reductase: synthesis and antiparasitic activity of 2, 4-diaminopteridine analogues with a bridged diarylamine side chain. J Med Chem 1999;42(23):4853-60
  • Cody V, Galitsky N, Luft JR, et al. Structure-based enzyme inhibitor design: modeling studies and crystal structure analysis of Pneumocystis carinii dihydrofolate reductase ternary complex with PT653 and NADPH. Acta Crystallogr D Biol Crystallogr 2002;58(6 Pt 2):946-54
  • Dana Farber Cancer Institute. WO2003031458 (2003)
  • Rosowsky A, Chen H, Fu H, Queener S. Synthesis of new 2,4-diaminopyrido[2,3-d]pyrimidine and 2,4-diaminopyrrolo[2,3-d]pyrimidine inhibitors of Pneumocystis carinii, Toxoplasma gondii and Mycobacterium avium dihydrofolate reductase. Bioorg Med Chem 2003;11:59-67
  • Gangjee A, Adair O, Queener S. Synthesis and biological evaluation of 2,4-diamino-6-(arylaminomethyl)pyrido[2,3-d]pyrimidines as inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase and as antiopportunistic infection and antitumor agents. J Med Chem 2003;46:5074-82
  • Gangjee A, Devraj R, Queener S. Synthesis and dihydrofolate reductase inhibitory activity of 2,4-diamino-5-deaza and 2,4-diamino-5,10-dideaza lipophilic antifolates. J Med Chem 1997;40:470-8
  • Duquesne Univ. of the Holy Ghost. US5346900 (1994)
  • Duquesne Univ. of the Holy Ghost. US5508281 (1996)
  • Duquesne Univ. of the Holy Ghost. US5736547 (1998)
  • Duquesne Univ. of the Holy Ghost. 5866580 (1999)
  • Duquesne Univ. of the Holy Ghost. US6114339 (2000)
  • Duquesne Univ. of the Holy Ghost. US6696455 B1 (2004)
  • Duquesne Univ. of the Holy Ghost. US5863920 (1999)
  • Duquesne Univ. of the Holy Ghost. US5958930 (1999)
  • Duquesne Univ. of the Holy Ghost. US6096750 (2000)
  • Duquesne Univ. of the Holy Ghost. US6962920 (2005)
  • Gangjee A, Devraj R, McGuire JJ, et al. Classical and nonclassical furo[2,3-d]pyrimidines as novel antifolates: synthesis and biological activities. J Med Chem 1994;37(8):1169-76
  • Gangjee A, Yu J, McGuire J, et al. Design, synthesis and X-ray crystal structure of a potent dual inhibitor of thymidylate synthase and dihydrofolate reductase as an antitumor agent. J Med Chem 2000;43:3837-51
  • Gangjee A, Guo X, Queener SF, et al. Selective Pneumocystis carinii dihydrofolate reductase inhibitors: design, synthesis, and biological evaluation of new 2,4-diamino-5-substituted-furo[2,3-d]pyrimidines. J Med Chem 1998;41(8):1263-71
  • Gangjee A, Zeng Y, McGuire JJ, Kisliuk RL. Effect of C9-methyl substitution and C8-C9 conformational restriction on antifolate and antitumor activity of classical 5-substituted 2,4-diaminofuro[2,3-d]pyrimidines. J Med Chem 2000;43(16):3125-33
  • Duquesne Univ. of the Holy Ghost. US6077844 (2000)
  • Duquesne Univ. of the Holy Ghost. US6420370 (2002)
  • Duquesne Univ. of the Holy Ghost. US5877178 (1999)
  • Duquesne Univ. of the Holy Ghost. US5939420 (1999)
  • Duquesne Univ. of the Holy Ghost. US6221872 (2001)
  • Gangjee A, Mavandadi F, Queener S. Effect of N9-methylation and bridge atom variation on the activity of 5-substituted 2,4-diaminopyrrolo[2,3-d]pyrimidines against dihydrofolate reductases from Pneumocystis carinii and Toxoplasma gondii. J Med Chem 1997;40:1173-7
  • Gangjee A, Mavandadi F, Queener S, McGuire J. Novel 2,4-diamino-5-substituted-pyrrolo[2,3-d]pyrimidines as classical and nonclassical antifolate inhibitors of dihydrofolate reductases. J Med Chem 1995;38:2158-65
  • Gangjee A, Lin X, Queener SF. Design, synthesis, and biological evaluation of 2,4-diamino-5-methyl-6-substituted-pyrrolo[2,3-d]pyrimidines as dihydrofolate reductase inhibitors. J Med Chem 2004;47(14):3689-92
  • Gangjee A, Lin X, Kisliuk RL, McGuire JJ. Synthesis of N-{4-[(2,4-diamino-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl)thio]benzoyl}-L-glutamic acid and N-{4-[(2-amino-4-oxo-5-methyl-4,7-dihydro-3H-pyrrolo[2,3-d]pyrimidin-6-yl) thio]benzoyl}-L-glutamic acid as dual inhibitors of dihydrofolate reductase and thymidylate synthase and as potential antitumor agents. J Med Chem 2005;48(23):7215-22
  • Duquesne Univ. of the Holy Ghost. US6103727 (2000)
  • Gangjee A, Vidwans A, Elzein E, et al. Synthesis, antifolate, and antitumor activities of classical and nonclassical 2-amino-4-oxo-5-substituted-pyrrolo[2,3-d]pyrimidines. J Med Chem 2001;44(12):1993-2003
  • Gangjee A, Mavandadi F, Kisliuk RL, et al. 2-amino-4-oxo-5-substituted-pyrrolo[2,3-d]pyrimidines as nonclassical antifolate inhibitors of thymidylate synthase. J Med Chem 1996;39(23):4563-8
  • Duquesne Univ. of the Holy Ghost. US6537999; 2003
  • Gangjee A, Yu J, McGuire JJ, et al. Design, synthesis, and X-ray crystal structure of a potent dual inhibitor of thymidylate synthase and dihydrofolate reductase as an antitumor agent. J Med Chem 2000;43(21):3837-51
  • Duquesne Univ. of the Holy Ghost. US6518426 (2003)

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.