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Review

Antimicrobial Dihydrofolate Reductase Inhibitors - Achievements and Future Options: Review

Pages 3-12 | Published online: 18 Jul 2013

REFERENCES

  • Buysse JM. The role of genomics in antibacterial drug discovery. Curr Med Chem 2001; 8: 1713–1726.
  • Missinou MA, Borrmann S, Schindler A, et al. Fosmidomycin for malaria. Lancet 2002; 360: 1941–1942.
  • Then RL. History and future of antimicrobial diaminopy-rimidines. J Chemother 1993; 5: 361–368.
  • Durand R, Savel J. Dihydrofolate reductase inhibitors: new developments in antiparasitic chemotherapy. Expert Opin Ther Patents 2001; 11: 1285–1290.
  • Myllykallio H, Lipowski G, Leduc D, Filee J, Forterre P, Liebl U. An alternative flavin-dependent mechanism for thymidylate synthesis. Science 2002; 297: 105–107.
  • Costi MP, Ferrari S. Update on antifolate drugs targets. Curr Drug Targets 2001; 2: 135–166.
  • Boggs AF, Hecker SJ. A tour of recent patent applica-tions addressing antibacterial resistance. Expert Opin Ther Patents 2002; 12: 1159–1172.
  • Gilbert, IH. Inhibitors of dihydrofolate reductase in leish-mania and trypanosomes. Biochim Biophys Acta 2002; 1587: 249–257.
  • Purcell WT, Ettinger TS. Novel antifolate drugs. Curr Oncol Rep 2003; 5: 114–125.
  • Kovacs JA, Gill VJ, Meshnik S, Masur H. New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia. JAMA 2001; 286: 2450–2460.
  • Periti P. Brodimoprim, a new bacterial dihydrofolate reductase inhibitor. J Chemother 1995; 7: 221–223.
  • McKeage K, Scott L. Atovaquone/Proguanil: A review of its use for the prophylaxis of Plasmodium falciparum malaria. Drugs 2003; 63: 597–623.
  • Mutabingwa T, Nzila A, Mberu E, et al. Chlorproguanil-dapsone for treatment of drug-resistant falci-parum malaria in Tanzania. Lancet 2001; 358: 1218–1223.
  • Klon AE, Hêroux A, Ross II, et al. Atomic structures of human dihydrofolate reductase corulexed with oNADPH and two lipophilic antifolates at 1.09 A and 1.05 A resolu-tion. J Mol Biol 2002; 320: 677–693.
  • Li R, Sirawaporn R, Chitnumsab P, et al. Three-dimensional structure of M. tuberculosis dihydrofolate reductase reveals opportunities for the design of novel tuberculosis drugs. J Mol Biol 2000; 295: 307–323.
  • Zuccotto F, Martin ACR, Laskowsky RA, Thornton JM, Gilbert IH. Dihydrofolate reductase: a potential drug target in trypanosomes and leishmania. J Comput Aided Mol Des 1998; 12: 241–257.
  • Cody V, Chan D, Galitsky N, et al. Structural studies on bioactive compounds. 30. Crystal structure and molecular modeling on the Pneumocystis carinii dihydrofolate reductase cofactor complex with TAB, a highly selective antifolate. Biochemistry 2000; 39: 3556–3564.
  • Delfino RT, Santos-Filho OA, Figueroa-Villar JD. Molecular modeling of wild type and antifolate resistant mutant Plasmodium falciparum DHFR. Biophys Chem 2002; 98: 287–300.
  • Yuvaniyama J, Chitnumsub P, Kamchonwongpaisan S, et al. Insights into antifolate resistance from malarial DHFR-TS structures. Nature Structural Biol 2003; 10: 357–365.
  • Marlowe CK, Selassie CD, Santi DV. Quantitative structure-activity relationships of the inhibition of Pneumocystis carinii dihydrofolate reductase by 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(X-phenyl)-s-triazines. J Med Chem 1995; 38: 967–972.
  • Debnath AK. Pharmacophore mapping of a series of 2,4-diamino-5-deazapteridine inhibitors of Mycobacterium auium complex dihydrofolate reductase. J Med Chem 2002; 45: 41–53.
  • Santos-Filho OA, Mishra RK, Hopfinger AJ. Free energy force field (FEFF) 3D-QSAR analysis of a set of Plasmodium falciparum dihydrofolate reductase inhibitors. J Computer-Aided Mol Des 2001; 15: 787–810.
  • Wyss PC, Gerber P, Hartman PG, et al. Novel dihydrofolate reductase inhibitors. Structure-based versus diversity-based library design and high-throughput synthesis and screen-ing. J Med Chem 2003; 46: 2304–2312.
  • Zolli-Juran M, Cechetto JD, Hartlen R, Daigle DM, Brown ED. High throughput screening identifies novel inhibitors of Escherichia coli dihydrofolate reductase that are competitive with dihydrofolate. Bioorg Med Lett 2003; 13: 2493–2496.
  • Then RL, Hartman PG, Kompis I, Stephan-Gtildner M, Stickel K. Epiroprim. Drugs Future 1994; 19: 446–449.
  • Lau H., Ferlan JT, Brophy VH, Rosowsky A, Hopkins-Sibley C. Efficacies of lipophilic inhibitors of dihydrofolate reductase against parasitic protozoa. Antimicrob Agents Chemother 2001; 45: 187–195.
  • Rosowsky A, Forsch RA, Queener SF. Inhibition of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium auium dihydrofolate reductases by 2,4-diamino-5-[2-methoxy-5-(omega-carboxyalkoxy)benzyl]pyrim-idines: marked improvement in potency relative to trimetho-prim and species selectivity relative to piritrexim. J Med Chem 2002; 45: 233–241.
  • Rosowsky A, Chen H, Fu H, Queener SF. Synthesis of new 2,4-diaminopyrido[2,3-d] pyrimidine and 2,4-diaminopy-rrolo[2,3-d]pyrimidine inhibitors of Pneumocystis carinii, Toxoplasma gondii, and Mycobacterium auium dihydrofolate reductase. Bioorganic Med Chem 2003; 11: 59–67.
  • 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 in AIDS. J Med Chem 2003; 46; 1726-1736.
  • Brophy VH, Vasquez J, Nelson RG, Forney JR, Rosowsky A, Hopkins-Sibley C. Identification of Cryptosporidium parvum dihydrofolate reductase inhibitors by complementation in Saccharomyces cereuisiae. Antimicrob Agents Chemother 2000; 44: 1019–1028.
  • Zhang K, Rathod PK. Divergent regulation of dihydrofolate reductase between malaria parasite and human host. Science 2002; 296: 545–547.
  • Whitlow M, Howard AJ, Stewart D, et al. X-ray crystal structures of Candida albicans dihydrofolate reductase: high resolution ternary complexes in which the dihydronicotinamide moiety of NADPH is displaced by an inhibitor. J Med Chem 2001; 44: 2928–2932.
  • Dale GE, Broger C, D'Arcy A, et al. A single amino acid substitution in Staphylococcus aureus dihydrofolate reductase determines trimethoprim resistance. J Mol Biol 1997; 266: 23–30.
  • Locher HH, Schlunegger H, Hartman PG, Angehrn P, Then RL. Antibacterial activities of epiroprim, a new dihydro-folate reductase inhibitor, alone and in combination with dapsone. Antimicrob Agents Chemother 1996; 40: 1376–1381.
  • Wyss PC, Guerry P, Hubschwerlen C, et al Anti-MRSA dihydrofolate reductase inhibitors: Synthesis and SAR. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy; San Francisco 26-29. September 1999; abstract 1800.
  • Locher HH, Wyss PC, Then RL, Hartman PG. Anti-MRSA dihydrofolate reductase inhibitors: biological characterization. 39th Interscience Conference on Antimicrobial Agents and Chemotherapy. San Francisco 26-29. September 1999; abstract 1801.
  • Adrian PV, Klugman KP. Mutations in the dihydrofolate reductase gene of trimethoprim-resistant isolates of Streptococcus pneumoniae. Antimicrob Agents Chemother 1997; 41: 2406–2413.
  • Hartman PG, Broger C, Caspers P, et al. The mechanism of trimethoprim resistance in Streptococcus pneumoniae. 37th Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto 28. September - 1. October 1997; abstract C-108
  • Maskell JP, Sefton AM, Hall LMC. Multiple mutations modulate the function of dihydrofolate reductase in trimetho-prim-resistant Streptococcus pneumoniae. Antimicrob Agents Chemother 2001; 45: 1104–1108.
  • Thielking DM, Destefano MS, Cynamon MH, Yeo AET. Enhanced in vitro activity of dihydrofolate reductase and dihydropteroate synthase inhibitors in combination against Nocardia spp. Antimicrob Agents Chemother 2003; 47: 1174.
  • Dosso M, Ouattara L, Cherif AM, Bouzid SA, Haller L, Fernex M. Experimental in vitro efficacy study on the interac-tion of epiroprim plus isoniazid against Mycobacterium tuber-culosis. Chemotherapy 2001; 47: 123–127.
  • Gerum AB, Ulmer JE, Jacobus DP, Jensen NP, Sherman DR, Sibley CH. Novel Saccharomyces cereuisiae screen identifies WR99210 analogues that inhibit Mycobacterium tuberculosis dihydrofolate reductase. Antimicrob Agents Chemother 2002; 46: 3362–3369.
  • Meyer SCC, Majumder SK, Cynamon MH. In vitro activities of P5-15, a new dihydrofolate reductase inhibitor, and its cyclic metabolite against Mycobacterium auium com-plex. Antimicrob Agents Chemother 1995; 39: 1862–1863.
  • Dhople AM. Antimicrobial activities of dihydrofolate reductase inhibitors, used singly or in combination with dap-sone, against Mycobacterium ulcerans. J Antimicrob Chemother 2001; 47: 93–96.
  • Dhople AM. In vitro activity of epiroprim, a dihydrofolate reductase inhibitor, singly and in combination with brodi-moprim and dapsone, against Mycobacterium leprae. Int J Antimicrob Agents 1999; 12: 319–323.
  • Dhople AM. In vivo activity of epiroprim, a dihydrofolate reductase inhibitor, singly and in combination with dap-sone, against Mycobacterium leprae. Int J Antimicrob Agents 2002; 19: 71–74.
  • Suling, WJ, Seitz LE, Pathak V, et al. Antimycobacterial activities of 2,4-Diamino-5-deazapteridine derivatives and effects on mycobacterial dihydrofolate reduc-tase. Antimicrob Agents Chemother 2000; 44: 2784-2793.
  • Kharkar PS, Kulkarni VM. A proposed model of Mycobacterium auium complex dihydrofolate reductase and its utility for drug design. Org Biomol Chem 2003; 1: 1315–1322.
  • Gangjee A, Adair O, Queener SF. Synthesis of 2,4-diamino-6-(thioarylmethyl)pyrido[2,3-d]pyrimidines as dihydro-folate reductase inhibitors. Bioorganic Med Chem 2001; 9: 2929-2935.
  • Gangjee A, Vidwans A, Elzein E, McGuire JJ, Queener SF, Kisliuk RL. Synthesis, antifolate, and antitumor activities of classical and nonclassical 2-amino-4-oxo-5-substituted-pyrro-lo[2,3-d]pyrimidines. J Med Chem 2001; 44: 1993-2003.
  • Chan DCM, Laughton CA, Queener SF, Stevens, MFG. Structural studies on bioactive compounds. Part 36: Design, synthesis and biological evaluation of pyrimethamine-based antifolates against Pneumocystis carinii. Bioorg Med Chem 2002; 10: 3001–3011.
  • Gschwend DA, Sirawaporn W, Santi DV, Kuntz ID. Specificity in structure-based drug design: identification of a novel, selective inhibitor of Pneumocystis carinii dihydrofolate reductase. Proteins: Structure, Function Genetics 1997; 29: 59–67.
  • Razavi B, Lund B, Allen BL, Schlesinger L. Failure of trimethoprim/sulfamethoxazole prophylaxis for Pneumocystis carinii pneumonia with concurrent leucovorin use. Infection 2002; 30: 41–42.
  • Safrin S, Lee BL, Sande MA. Adjunctive folinic acid with trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia in AIDS patients is associated with an increased risk of therapeutic failure and death. J Infect Dis 1994; 170: 912–917.
  • Castaldo RA, Gump DW, McCormack JJ. Acvtivity of 2,4-diaminoquinazoline compounds against Can dida species. Antimicrob Agents Chemothe. 1979; 15: 81–86.
  • Chan JH, Hong JS, Kuiper LF, et al. Selective inhibitors of Candida albicans dihydrofolate reductase: activity and selectivity of 5-(arylthio)-2,4-diaminoquinazolines. J Med Chem 1995; 38: 3608–3616.
  • Mockenhaupt FP, Eggelte TA, Bohme T, Thompson WNA, Bienzle U. Plasmodium falciparum dihydrofolate reductase and pyrimethamine use in pregnant Ghanaian women. Am J Trop Med Hyg 2001; 65: 21–26.
  • Durand R, Eslahpazire J, Jafari S, et al. Use of molecular beacons to detect an antifolate resistance-associated muta-tion in Plasmodium falciparum. Antimicrob Agents Chemother 2000; 44: 3461–3464.
  • Tarnchompoo B, Sirichaiwat C, Phupong W, et al. Development of 2,4-diaminopyrimidines as antimalarials based on inhibition of the 5108N and C59R + 5108N mutants of dihydrofolate reductase from pyrimethamine-resistant Plasmodium falciparum. J Med Chem 2002; 45: 1244–1252.
  • Vilaivan T, Saesaengseerung N, Jarprung D, Kamchonwongpaisan S, Sirawaraporn W, Yuthavong Y. Synthesis of solution-phase combinatorial library of 4,6-diamino-1,2-dihydro-1,3,5-triazine and identification of new leads against A16V + 5108T mutant dihydrofolate reductase of Plasmodium falciparum. Bioorganic Med Chem 2003; 11: 217–224.
  • Mberu EK, Nzila AM, Nduati E, et al. Plasmodium falciparum: in vitro activity of sulfadoxine and dapsone in field isolates from Kenya: point mutations in dihydropteroate syn-thase may not be the only determinants in sulfa resistance. Exptl Parasitol 2002; 101: 90–96.
  • Reynolds MG, Oh J, Roos DS. In vitro generation of novel pyrimethamine mutations in the Toxoplasma gondii dihydrofolate reductase. Antimicrob Agents Chemother 2001; 45: 1271–1277.
  • Chang HR, Arsenijewic D, Comte R, Polak A, Then RL, Pechère JC. Activity of epiroprim (Ro 11-8958), a dihy-drofolate reductase inhibitor, alone and in combination with dapsone against Toxoplasma gondii. Antimicrob Agents Chemother 1994; 38: 1803–1807.
  • Zuccotto F, Zvelebil M, Brun R, et al. Novel inhibitors of Trypanosoma cruzi dihydrofolate reductase. Eur J Med Chem 2001; 36: 395–405.
  • Hurtado-Guerrero R, Pena-Diaz J, Montalvetti A, Perez-Ruiz LM, Gonzales-Pacanowska D. Kinetic properties and inhibition of Trypanosoma cruzi 3-hydroxy-3-methylglu-taryl CoA reductase. FESS Lett 2002; 510: 141–144.
  • Balana-Fouce R, Reguera, RM, Cubria, JC, Ordemez, D. The pharmacology of leishmaniasis. Gen Pharmac 1998; 30: 435–443.
  • Chowdhury SF, Villamor VB, Guerrero RH, et al. Design, synthesis, and evaluation of inhibitors of trypanosomal and leishmanial dihydrofolate reductase. J Med Chem 1999; 42: 4300–4312.
  • Chowdhury SF, Lucrezia RD, Guerrero RH, et al. Novel inhibitors of Leishmanial dihydrofolate reductase. Bioorg Med Chem Lett 2001; 11: 977–980.
  • McKie JH. Homology modeling of the dihydrofolate reductase-thymidylate synthase bifunctional enzyme of Leishmania major, a potential target for rational drug design in leishmaniasis. Drug Des Discov 1994; 11: 269–288.
  • Berman JD, King M, Edwards N. Antileishmanial activities of 2,4-diaminoquinazoline putative dihydrofolate reductase inhibitors. Antimicrob Agents Chemother 1989; 33: 1860-1863.
  • Lye LF, Cunningham ML, Beverley SM. Characterization of quinoid-dihydropteridine reductase (QDPR) from the lower eukaryote Leishmania major. J Biol Chem 2002; 277: 38245–38253.
  • Nare B, Hardy LW, Beverley SM. The roles of pteridine reductase 1 and dihydrofolate reductase-thymidylate syn-thase in pteridine metabolism in the protozoan parasite Leishmania major. J Biol Chem 1997; 272: 13883–13891.
  • Cunningham ML, Beverley SM. Pteridine salvage throughout the Leishmania infectious cycle: implications for antifolate chemotherapy. Mol Biochem Parasitol 2001; 113: 199–213.
  • Washtien WL, Grumont R, Santi DV. DNA amplification in antifolate-resistant Leishmania. The thymidylate-syn-thase-dihydrofolate reductase gene and abundant mRNAs. J Biol Chem 1985; 260: 7809–7812.
  • Nelson RG, Rosowsky A. Dicyclic and tricyclic diaminopyrimidine derivatives as potent inhibitors of Cryptosporidium parvum dihydrofolate reductase: Structure-activity and structure-selectivity correlations. Antimicrob Agents Chemother 2001; 45: 3293–3303.
  • Huang YL, Lin CF, Lee YJ, et al. Non-classical antifolates, 5-(N-phenylpyrrolidin-3y1)-2,4,6-triaminopyrimidines and 2,4-diamino-6(51-I)-oxopyrimidines, synthesis and antitumor studies. Bioorg Med Chem 2003; 11: 145–157.
  • Walker VK, Tyshenko MG, Kuiper MJ, et al. Tobacco budworm dihydrofolate reductase is a promising target for insecticide discovery. Eur J Biochem 2000; 267: 394–403.
  • Elvin CM, Liyou NE, Pearson R, Kemp DH, Dixon NE. Molecular cloning and expression of the dihydrofolate reduc-tase (DHFR) gene from adult buffalo fly (Haematobia irritans exigua): effects of antifolates. Insect Mol Biol 2003; 12: 173–183.

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