Structure-activity relationships of C6-uridine derivatives targeting Plasmodia orotidine monophosphate decarboxylase

Journal of Medicinal Chemistry

Volumn 51, Issue 3, 2008, Pages 439-448

  Bello, Angelica M ^a   Poduch, Ewa ^a   Liu, Yan ^d   Wei, Lianhu ^a   Crandall, Ian ^b,d   Wang, Xiaoyang ^a   Dyanand, Christopher ^a,b   Kain, Kevin C ^b,d   Pai, Emil F ^c,d   Kotra, Lakshmi P ^a,b,e  

^a UNIVERSITY HEALTH NETWORK   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c PRINCESS MARGARET HOSPITAL   (Canada)

^d UNIVERSITY OF TORONTO   (Canada)

^e UNIVERSITY OF NORTH CAROLINA AT GREENSBORO   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 AMINOURIDINE MONOPHOSPHATE; 6 AZIDOURIDINE MONOPHOSPHATE; 6 CYANOURIDINE MONOPHOSPHATE; 6 IODOURIDINE; 6 METHYLURIDINE MONOPHOSPHATE; 6 N METHYLAMINOURIDINE MONOPHOSPHATE; 6 N,N DIMETHYLAMINOURIDINE MONOPHOSPHATE; C6 URIDINE DERIVATIVE; OROTIDINE 5' PHOSPHATE DECARBOXYLASE; UNCLASSIFIED DRUG; URIDINE DERIVATIVE; URIDINE PHOSPHATE;

ANIMAL CELL; ANTIMALARIAL ACTIVITY; ARTICLE; CONTROLLED STUDY; COVALENT BOND; DRUG POTENCY; ENZYME BINDING; ENZYME INHIBITION; ENZYME SYNTHESIS; MALARIA; MULTIDRUG RESISTANCE; NONHUMAN; PLASMODIUM; STRUCTURE ACTIVITY RELATION;

ANIMALS; ANTIMALARIALS; CHO CELLS; CRICETINAE; CRICETULUS; CRYSTALLOGRAPHY, X-RAY; MODELS, MOLECULAR; OROTIDINE-5'-PHOSPHATE DECARBOXYLASE; PLASMODIUM; PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; STRUCTURE-ACTIVITY RELATIONSHIP; URIDINE; URIDINE MONOPHOSPHATE;

EID: 39149112528     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm7010673     Document Type: Article

References (37)

1. Biagini, G. A.; O'Neill, P. M.; Bray, P. G.; Ward, S. A. Current drug development portfolio for antimalarial therapies. Curr. Opin. Pharmacol. 2005, 5, 473-478.
2. Cunha-Rodrigues, M.; Prudencio, M.; Mota, M. M.; Haas, W. Antimalarial drugs-host target (re)visited. Biotechnol. J. 2006, 1, 321-332.
3. Rathore, D.; McCutchan, T. F.; Sullivan, M.; Kumar, S. Antimalarial drugs: Current status and new developments. Expert Opin. Invest. Drugs 2005, 14, 871-883.
4. Linares, G. E.; Rodriguez, J. B. Current status and progresses made in malaria chemotherapy. Curr. Med. Chem. 2007, 14, 289-314.
5. Bathurst, I.; Hentschel, C. Medicines for malaria venture: Sustaining antimalarial drug development. Trends Parasitol. 2006, 22, 301-307.
6. Vangapandu, S.; Jain, M.; Kaur, K.; Patil, P.; Patel, S. R.; Jain, R. Recent advances in antimalarial drug development. Med. Chem. Rev. 2007, 27, 65-107.
7. Gero, A. M.; O'Sullivan, W. J. Purines and pyrimidines in malarial parasites. Blood Cells 1990, 16, 467-484.
8. Gardner, M. J.; Hall, N.; Fung, E.; White, O.; Berriman, M.; Hyman, R. W.; Carlton, J. M.; Pain, A.; Nelson, K. E.; Bowman, S.; Paulsen, I. T.; James, K.; Eisen, J. A.; Rutherford, K.; Salzberg, S. L.; Craig, A.; Kyes, S.; Chan, M. S.; Nene, V.; Shallom, S. J.; Suh, B.; Peterson, J.; Angiuoli, S.; Pertea, M.; Allen, J.; Selengut, J.; Haft, D.; Mather, M. W.; Vaidya, A. B.; Martin, D. M.; Fairlamb, A. H.; Fraunholz, M. J.; Roos, D. S.; Ralph, S. A.; McFadden, G. I.; Cummings, L. M.; Subramanian, G. M.; Mungall, C.; Venter, J. C.; Carucci, D. J.; Hoffman, S. L.; Newbold, C.; Davis, R. W.; Fraser, C. M.; Barrell, B. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 2002, 419, 498-511.
9. Pink, R.; Hudson, A.; Mouries, M. A.; Bendig, M. Opportunities and challenges in antiparasitic drug discovery. Nat. Rev. Drug Discovery 2005, 4, 727-740.
10. Jones, M. E. Pyrimidine nucleotide biosynthesis in animals: Genes, enzymes, and regulation of UMP biosynthesis. Annu. Rev. Biochem. 1980, 49, 253-279.
11. Mehta, S. R.; Das, S. Management of malaria: Recent trends. J. Commun. Dis. 2006, 38, 130-138.
12. Kremsner, P. G.; Krishna, S. Antimalarial combinations. Lancet 2004, 364, 285-294.
13. Nwaka, S.; Hudson, A. Innovative lead discovery strategies for tropical diseases. Nat. Rev. Drug Discovery 2006, 5, 941-955.
14. Jana, S.; Paliwal, J. Novel molecular targets for antimalarial chemotherapy. Int. J. Antimicrob. Agents 2007, 30, 4-10.
15. Biagini, G. A.; O'Neill, P. M. O.; Bray, P. G.; Ward, S. A. Current drug development portfolio for antimalarial therapies. Curr. Opin. Pharmacol. 2005, 5, 473-478.
16. Miller, B. G.; Wolfenden, R. Catalytic proficiency: The unusual case of OMP decarboxylase. Annu. Rev. Biochem. 2002, 71, 847-885.
17. Sievers, A.; Wolfenden, R. Equilibrium of formation of the 6-carbanion of UMP, a potential intermediate in the action of OMP decarboxylase. J. Am. Chem. Soc. 2002, 124, 13986-13987.
18. Snider, M. J.; Wolfenden. R. The rate of spontaneous decarboxylation of amino acids. J. Am. Chem. Soc. 2000, 122, 11507-11508.
19. Seymour, K. K.; Lyons, S. D.; Phillips, L.; Rieckmann, K. H.; Christopherson, R. I. Cytotoxic effects of inhibitors of de novo pyrimidine biosynthesis upon Plasmodium falciparum. Biochemistry 1994, 33, 5268-5274.
20. Christopherson, R. I.; Lyons, S. D.; Wilson, P. K. Inhibitors of de novo nucleotide biosynthesis as drugs. Acc. Chem. Res. 2002, 35, 961-971.
21. Krungkrai, J.; Krungkrai, S. R.; Phakanont, K. Antimalarial activity of orotate analogs that inhibit dihydroorotase and dihydroorotate dehydrogenase. Biochem. Pharmacol. 1992, 43, 1295-1301.
22. Scott, H. V.; Gero, A. M.; O'Sullivan, W. J. In vitro inhibition of Plasmodium falciparum by Pyrazofurin, an inhibitor of pyrimidine biosynthesis de novo. Mol. Biochem. Parasitol. 1986, 18, 3-15.
23. Fujihashi, M.; Bello, A. M.; Poduch, E.; Wei, L.; Annedi, S. C.; Pai, E. F.; Kotra, L. P. An unprecedented twist to ODCase catalytic activity. J. Am. Chem. Soc. 2005, 127, 15048-15050.
24. Poduch, E.; Bello, A. M.; Tang, S.; Fujihashi, M.; Pai, E. F.; Kotra, L. P. Design of inhibitors of orotidine monophosphate decarboxylase using bioisosteric replacement and determination of inhibition kinetics. J. Med. Chem. 2006, 49, 4937-4945.
25. Kotra, L. P.; Pai, E. F.; Bello, A. M.; Fujihashi, M.; Poduch, E. Inhibitors of orotidine monophosphate decarboxylase (ODCase) activity. U.S. Patent Application 60/596,537, 2005,patent pending.
26. Bello, A. M.; Poduch, E.; Fujihashi, M.; Amani, M.; Li, Y.; Crandall, I.; Hui, R.; Lee, P. I.; Kain, K. C.; Pai, E. F.; Kotra, L. P. A potent, covalent inhibitor of orotidine 5′-monophosphate decarboxylase with antimalarial activity. J. Med. Chem. 2007, 50 (5), 915-921.
27. Wu, N.; Mo, Y.; Gao, J.; Pai, E. F. Electrostatic stress in catalysis: structure and mechanism of the enzyme orotidine monophosphate decarboxylase. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 2017-2022.
28. i. Biochem. J. 1972, 129, 197-202.
29. Trager, W.; Jensen, J. Human malaria parasites in continuos culture. Science 1976, 193, 673-675.
30. Smilkstein, M.; Sriwilaijaroen, N.; Kelly, J. X.; Wilairat, P.; Riscoe, M. Simple and inexpensive fluorescence-based technique for high-throughput antimalarial drug screening. Antimicrob. Agents Chemother. 2004, 48, 1803-1806.
31. Campling, B. G.; Pym, J.; Galbraith, P. R.; Cole, S. P. Use of MTT assay for rapid determination of chemosensitivity of human leukemic blast cells. Leuk. Res. 1988, 12, 823-831.
32. Otwinowski, Z.; Minor, W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 1997, 276, 307-326.
33. Vagin, A.; Teplyakov, A. MOLREP: An automated program for molecular replacement. J. Appl. Crystallogr. 1997, 30, 1022-1025.
34. Murshudov, G. N.; Vagin, A. A.; Dodson, E. J. Refinement of macromolecular structures by the maximum-likehood method. Acta Crystallogr. 1997, D53, 240-255.
35. Emsley, P.; Cowtan, K. Model building tools for molecular graphics. Acta Crystallogr. 2004, D60, 2126-2132.
36. SYBYL 7.0, Tripos Inc.: 1699 South Hanley Rd., St. Louis, Missouri, 63144.
37. Tan, X.; Chu, C. K.; Boudinot, F. D. Development and optimization of anti-HIV nucleoside analogs and prodrugs: A review of their cellular pharmacology, structure-activity relationships, and pharmacokinetics. Adv. Drug Delivery Rev. 1999, 39, 117-151.