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Research Article

Synthesis and biological evaluation of biguanide and dihydrotriazine derivatives as potential inhibitors of dihydrofolate reductase of opportunistic microorganisms

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Pages 331-339 | Received 12 Mar 2009, Accepted 27 May 2009, Published online: 29 Oct 2009

References

  • Chan DCM, Anderson AC. Towards species-specific antifolates. Curr Med Chem 2006;13:377–98.
  • Gangjee A, Kurup S, Namjoshi O. Dihydrofolate reductase as a target for chemotherapy in parasites. Curr Pharm Design 2007;13:609–39.
  • Gangjee A, Yang J, Queener SF. Novel non-classical C9-methyl-5-substituted-2,4-diaminopyrrolo-[2,3-d]pyrimidines as potential inhibitors of dihydrofolate reductase and as anti-opportunistic agents. Bioorg Med Chem 2006;14:8341–51.
  • Gangjee A, Adair OO, Pagley M, Queener SF. N9-substituted 2,4-diaminoquinazolines: synthesis and biological evaluation of lipophilic inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase. J Med Chem 2008;49:6195–200.
  • Pelphrey PM, Popov VM, Joska TM, Beierlein JM, Bolstad ESD, Fillingham YA, et al. Highly efficient ligands for dihydrofolate reductase from Cryptosporidium hominis and Toxoplasma gondii inspired by structural analysis. J Med Chem 2007;50:940–50.
  • Dasgupta T, Chitnumsub P, Kamchonwongpaisan S, Maneeruttanarungroj C, Nichols SE, Lyons TM, et al. Exploiting structural analysis, in silico screening, and serendipity to identify novel inhibitors of drug-resistant falciparum malaria. ACS Chem Biol 2009;4:29–40.
  • Martucci WE, Udier-Blagovic M, Atreya C, Babatunde O, Vargo MA, Jorgensen WL, et al. Novel non-active site inhibitor of Cryptosporidium hominis TS-DHFR identified by a virtual screen. Bioorg Med Chem Lett 2009;19:418–23.
  • Blaney JM, Hansch C, Silipo C, Vittoria A. Structure-activity relationships of dihydrofolated reductase inhibitors. Chem Rev 1984;84:333–407.
  • Kidwai M, Mothsra P, Mohan R, Biswas S. 1-Aryl-4,6-diamino-1,2-dihydrotriazine as antimalarial agent: a new synthetic route. Bioorg Med Chem Lett 2005;15:915–17.
  • Baker BR, Janson EE. Irreversible enzyme inhibitors. CLV. Active-site-directed irreversible inhibitors of dihydrofolic reductase derived from 1-[4-omega-aminoalkoxy)-3-chlorophenyl]-4,6-diamino-1,2-dihydro-2,2-dimethyl-s-triazines bearing a terminal sulfonyl fluoride. J Med Chem 1969;12:672–6.
  • Lee HK, Chui WK. Combinatorial mixture synthesis and biological evaluation of dihydrophenyl triazine antifolates. Bioorg Med Chem 1999;7:1255–62.
  • Mayer S, Daigle DM, Brown ED, Khatri J, Organ MG. An expedient and facile one-step synthesis of a biguanide library by microwave irradiation coupled with simple product filtration. Inhibitors of dihydrofolate reductase. J Comb Chem 2004;6:776–82.
  • Jensen NP, Ager AL, Bliss RA, Canfield CJ, Kotecka BM, Rieckmann KH, et al. Phenoxypropoxybiguanides, prodrugs of DHFR-inhibiting diaminotriazine antimalarials. J Med Chem 2001;44:3925–31 (and references therein).
  • Broughton MC, Queener SF. Pneumocystis carinii dihydrofolate reductase used to screen potential antipneumocystis drugs. Antimicrob Agents Chemother 1991;35:1348–55.
  • Chio LC, Queener SF. Identification of highly potent and selective inhibitors of Toxoplasma gondii dihydrofolate reductase. Antimicrob Agents Chemother 1993;37:1914–23.
  • Kuyper L, Roth B, Baccanari D, Ferone R, Bedell CR, Campness JN, et al. Receptor-based design of dihydrofolate reductase inhibitors: comparison of crystallographically determined enzyme binding with enzyme affinity in a series of carboxy-substituted trimethoprim analogs. J Med Chem 1982;25:1120–3.
  • Chan DCM, Fu H, Forsch RA, Queener SF, Rosowsky A. Design, synthesis, and antifolate activity of new analogues of piritrexim and other diaminopyrimidine dihydrofolate reductase inhibitors with ω-carboxyalkoxy or ω-carboxy-1-alkynyl substitution in the side chain. J Med Chem 2005;48:4420–31 (and references therein).
  • Otzen T, Wempe EG, Kunz B, Bartels R, Lehwark-Yvetot G, Hänsel W, et al. Folate-synthesizing enzyme system as target for development of inhibitors and inhibitor combinations against Candida albicans—Synthesis and biological activity of new 2,4-diaminopyrimidines and 4’-substituted 4-aminodiphenyl sulfones. J Med Chem 2004;47:240–53.
  • Bag S, Tawari NR, Degani MS. Insight into inhibitory activity of mycobacterial dihydrofolate reductase inhibitors by in-silico molecular modeling approaches. QSAR Comb Sci 2009;3:296–311.
  • Allen CFH, Gates JW. o-n-Butoxynitrobenzene. Organic Synth 1945;25:9.
  • Salzberg PL, Supniewski JV. β-Bromoethylphthalimide. Organic Synth 1927;7:8.
  • Baker BR, Ho B-T. Analogs of tetrahydrofolic acid. xxix. Hydrophobic bonding to dihydrofolic reductase. ii. On the mode of phenyl binding of 1-aryl-4,6-diamino-1,2-dihydro-2,2-dimethyl-s-triazines. J Heterocycl Chem 1965;2:335–9.
  • Modest EJ., Chemical,and biological studies on 1,2-dihydro-s-triazines., II. Three-component synthesis. J Org Chem 1956;21:1–13.
  • Glide, version 5.0. New York: Schrödinger, LLC, 2008.
  • LigPrep, version 3.0. New York: Schrödinger, LLC, 2008.

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