Pyrimido-pyrimidines: A novel class of dihydrofolate reductase inhibitors

Food Technology and Biotechnology

Volumn 47, Issue 3, 2009, Pages 236-245

  Banjanac, Mihailo ^a   Tatic, Iva ^a   Ivezic, Zrinka ^b   Tomic, Sanja ^c   Dumic, Jerka ^d  

^a GLAXOSMITHKLINE   (United Kingdom)

^b Nabriva Therapeutics Inc   (Austria)

^c RUDER BO KOVI INSTITUTE   (Croatia)

^d UNIVERSITY OF ZAGREB   (Croatia)

Author keywords

Dihydrofolate reductase; Docking; Inhibitors; Pyrimido 4,5 d pyrimidine 2,4 diamine; Structure activity relationship

Indexed keywords

ANTIBACTERIAL PROPERTIES; DIFFERENT CLASS; DIHYDROFOLATE REDUCTASE; DOCKING STUDIES; PYRIMIDO[4,5-D]PYRIMIDINE-2,4-DIAMINE; SMALL MOLECULES; STRUCTURAL MOTIFS; STRUCTURE ACTIVITY RELATIONSHIPS;

CORROSION INHIBITORS; DOCKING; ENZYMES;

AROMATIC COMPOUNDS;

BACTERIA (MICROORGANISMS); TETRA;

EID: 70349387898     PISSN: 13309862     EISSN: 13342606     Source Type: Journal    
DOI: None     Document Type: Article

References (26)

1. A. Gangjee, W. Li, J. Yang, R.L. Kisliuk, Design, synthesis, and biological evaluation of classical and nonclassical 2-amino-4-oxo-5-substituted-6-methylpyrrolo[3,2-d]pyrimidines as dual thymidylate synthase and dihydrofolate reductase inhibitors, J. Med. Chem. 51 (2008) 68-76.
2. J. Feng, S. Goswami, E.E. Howell, R67, the other dihydrofolate reductase: Rational design of an alternate active site configuration, Biochemistry, 47 (2008) 555-565.
3. B.I. Schweitzer, A.P. Dicker, J.R. Bertino, Dihydrofolate reductase as a therapeutic target, FASEB J. 4 (1990) 2441- 2452.
4. A. Gangjee, H.D. Jain, S. Kurup, Recent advances in classical and non-classical antifolates as antitumor and antiopportunistic infection agents: Part I, Anticancer Agents Med. Chem. 7 (2007) 524-542.
5. A. Gangjee, H.D. Jain, S. Kurup, Recent advances in classical and non-classical antifolates as antitumor and antiopportunistic infection agents: Part II, Anticancer Agents Med. Chem. 8 (2008) 205-231.
6. A. Gangjee, S. Kurup, O. Namjoshi, Dihydrofolate reductase as a target for chemotherapy in parasites, Curr. Pharm. Des. 13 (2007) 609-639.
7. I.M. Kompis, K. Islam, R.L. Then, DNA and RNA synthesis: Antifolates, Chem. Rev. 105 (2005) 593-620.
8. J.J. Burchall, G.H. Hitchings, Inhibitor binding analysis of dihydrofolate reductases from various species, Mol. Pharmacol. 1 (1965) 126-136.
9. B.A. Sampson, R. Misra, S.A. Benson, Identification and characterization of a new gene of Escherichia coli K-12 involved in outer membrane permeability, Genetics, 122 (1989) 491-501.
10. K.F. Jensen, The Escherichia coli K-12 'wild types' W3110 and MG1655 have an rph frameshift mutation that leads to pyrimidine starvation due to low pyrE expression levels, J. Bacteriol. 175 (1993) 3401-3407.
11. E.E. Howell, P.G. Foster, L.M. Foster, Construction of a dihydrofolate reductase-deficient mutant of Escherichia coli by gene replacement, J. Bacteriol. 170 (1988) 3040-3045.
12. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, NCCLS, M7-A7 26, Wayne, PA, USA (2003)
13. T. Mosmann, Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays, J. Immunol. Methods, 65 (1983) 55-63.
14. M.R. Sawaya, J. Kraut, Loop and subdomain movements in the mechanism of Escherichia coli dihydrofolate reductase: Crystallographic evidence, Biochemistry, 36 (1997) 586-603.
15. A.E. Klon, A. Héroux, L.J. Ross, V. Pathak, C.A. Johnson, J.R. Piper, D.W. Borhani, Atomic structures of human di-hydrofolate reductase complexed with NADPH and two lipophilic antifolates at 1.09 Å and 1.05 Å resolution, J. Mol. Biol. 320 (2002) 677-693.
16. G. Jones, P. Willett, R.C. Glen, A.R. Leach, R. Taylor, Development and validation of a genetic algorithm for flexible docking, J. Mol. Biol. 267 (1997) 727-748.
17. J. Wang, R.M. Wolf, J.W. Caldwell, P.A. Kollman, D.A. Case, Development and testing of a general Amber force field, J. Comput. Chem. 25 (2004) 1157-1174.
18. Amber10, The Amber Molecular Dynamics Package, University of California, San Francisco, CA, USA (2008) (http://ambermd.org).
19. Y. Duan, C. Wu, S. Chowdhury, M.C. Lee, G. Xiong, W. Zhang, R. Yang, P. Cieplak, R. Luo, T. Lee, J. Caldwell, J. Wang, P. Kollman, A point-charge force field for molecular mechanics simulations of proteins based on condensed-phase quantum mechanical calculations, J. Comput. Chem. 24 (2003) 1999-2012.
20. M.W. Mahoney, W.L. Jorgensen, A five-site model for liquid water and the reproduction of the density anomaly by rigid, nonpolarizable potential functions, J. Chem. Phys. 112 (2000) 8910-8922.
21. T. Darden, D. York, L. Pedersen, Particle mesh Ewald - An NlogN method for Ewald sums in large systems, J. Chem. Phys. 98 (1993) 10089-10092.
22. A. Gangjee, A. Vasudevan, S.F. Queener, R.L. Kisliuk, 6-substituted 2,4-diamino-5-methylpyrido[2,3-d]pyrimidines as inhibitors of dihydrofolate reductases from Pneumocystis carinii and Toxoplasma gondii and as antitumor agents, J. Med. Chem. 38 (1995) 1778-1785.
23. A. Gangjee, A. Vasudevan, S.F. Queener, Synthesis and biological evaluation of nonclassical 2,4-diamino-5-methylpyrido[2,3-d]pyrimidines with novel side chain substituents as potential inhibitors of dihydrofolate reductases, J. Med. Chem. 40 (1997) 479-485.
24. J.R. Piper, C.A. Johnson, C.A. Krauth, R.L. Carter, C.A. Hosmer, S.F. Queener, S.E. Borotz, E.R. Pfefferkorn, Lipophilic antifolates as agents against opportunistic infections. 1. Agents superior to trimetrexate and piritrexim against Toxoplasma gondii and Pneumocystis carinii in in vitro evaluations, J. Med. Chem. 39 (1996) 1271-1280.
25. A. Gangjee, A.P. Vidwans, A. Vasudevan, S.F. Queener, R.L. Kisliuk, V. Cody, R. Li, N. Galitsky, J.R. Luft, W. Pangborn, Structure-based design and synthesis of lipophilic 2,4-diamino-6-substituted quinazolines and their evaluation as inhibitors of dihydrofolate reductases and potential antitumor agents, J. Med. Chem. 41 (1998) 3426-3434.
26. A. Gangjee, A. Vasudevan, S.F. Queener, R.L. Kisliuk, 2,4-diamino-5-deaza-6-substituted pyrido[2,3-d]pyrimidine antifolates as potent and selective nonclassical inhibitors of dihydrofolate reductases, J. Med. Chem. 39 (1996) 1438-1446.