A three-dimensional in silico pharmacophore model for inhibition of Plasmodium falciparum cyclin-dependent kinases and discovery of different classes of novel Pfmrk specific inhibitors

Journal of Medicinal Chemistry

Volumn 47, Issue 22, 2004, Pages 5418-5426

  Bhattacharjee, Apurba K ^a   Geyer, Jeanne A ^a   Woodard, Cassandra L ^a   Kathcart, April K ^a   Nichols, Daniel A ^a   Prigge, Sean T ^b   Li, Zhiyu ^a   Mott, Bryan T ^a   Waters, Norman C ^a  

^a WALTER REED ARMY INSTITUTE OF RESEARCH   (United States)

^b JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

(4 CHLOROPHENYL) [3 (4 CHLOROPHENYL) 2,4 DIOXOOXAZOLIDIN 5 YLIDENE]ACETONITRILE; 1 (2,4 DICHLOROBENZOYL) 3 (2 HYDROXY 5 NITROPHENYL)THIOUREA; 1 (3 NITROPHENYL) 3 PHENYLPROPENONE; 1 (4 NITROPHENYL) 3 PYRIDIN 2 YLPROPENONE; 2 [(2 HYDROXYETHYL)[5 (4 METHOXYPHENYL)[1,3,4]OXADIAZOL 2 YL]AMINO]ETHANOL; 2 CHLORO N (4 CHLOROBENZOTHIAZOL 2 YL)ACETAMIDE; 2 PYRIDIN 2 YLMETHYLENE 3,4 DIHYDRO 2H NAPHTHALEN 1 ONE; 3 OXO 1 PHENYL 1,3 DIHYDROISOBENZOFURAN 1 YLTHIOUREA; 3,9,11 TRICHLORO 5,6 DIHYDROBENZO[C]ACRIDINE 7 CARBONYL; 4 AZA 8 FLUOROINDOLO[2,1 B]QUINAZOLINE 6,12 DIONE; 4 AZA 9 CHLOROINDOLO[2,1 B]QUINAZOLINE 6,12 DIONE; 5 CHLORO 4 NITROTHIOPHENE 2 SULFONIC ACID (4 TRIFLUOROMETHYLPHENYL)AMIDE; ADENOSINE TRIPHOSPHATE; ANTIMALARIAL AGENT; CYCLIN DEPENDENT KINASE; CYCLIN DEPENDENT KINASE 2; CYCLIN DEPENDENT KINASE INHIBITOR; ETHYL 2 (4 NITROBENZOYL) 3 PYRIDIN 2 YLACRYLATE; ETHYL 2 CHLORO 5 NITROBENZOATE; N (4 CHLORO 2 METHYLPHENYL) 3 NITROBENZAMIDE; N [4 (3 PHENYLACRYLOYL)PHENYL]ACETAMIDE; UNCLASSIFIED DRUG;

ARTICLE; CELL DIVISION; DRUG POTENCY; DRUG TARGETING; ENZYME ASSAY; ENZYME INHIBITION; EUKARYOTE; HYDROGEN BOND; HYDROPHOBICITY; NONHUMAN; PHARMACOPHORE; PLASMODIUM FALCIPARUM; QUANTITATIVE STRUCTURE ACTIVITY RELATION; REGULATORY MECHANISM; X RAY CRYSTALLOGRAPHY;

ADENOSINE TRIPHOSPHATE; ANIMALS; ANTIMALARIALS; BINDING SITES; CYCLIN-DEPENDENT KINASES; DATABASES, FACTUAL; HYDROGEN BONDING; HYDROPHOBICITY; MODELS, MOLECULAR; PLASMODIUM FALCIPARUM; PROTEIN KINASES; PROTOZOAN PROTEINS; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 6044260115     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm040108f     Document Type: Article

References (37)

1. Breman, J. G. The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden. Am. J. Trop. Med. Hyg. 2001, 64, 1-11.
2. Winstanley, P. A.; Ward, S. A.; Snow, R. W. Clinical status and implications of antimalarial drug resistance. Microbes Infect. 2002, 4, 157-164.
3. Meijer, L.; Leclerc, S.; Leost, M. Properties and potential-applications of chemical inhibitors of cyclin-dependent kinases. Pharmacol. Ther. 1999, 82, 279-284.
4. Fischer, P. M.; Lane, D. P. Inhibitors of Cyclin-Dependent Kinases as Anti-Cancer Therapeutics. Curr. Med. Chem. 2000, 7, 1213-1245 [Record as supplied by publisher].
5. O'Hare, M.; Wang, F.; Park, D. S. Cyclin-dependent kinases as potential targets to improve stroke outcome. Pharmacol. Ther. 2002, 93, 135-143.
6. Monaco, E. A., 3rd; Vallano, M. L. Cyclin-dependent kinase inhibitors: cancer killers to neuronal guardians. Curr. Med. Chem. 2003, 10, 367-379.
7. Ivorra, C.; Samyn, H.; Edo, M. D.; Castro, C.; Sanz-Gonzalez, S. M.; et al. Inhibiting cyclin-dependent kinase/cyclin activity for the treatment of cancer and cardiovascular disease. Curr. Pharm. Biotechnol. 2003, 4, 21-37.
8. Knockaert, M.; Greengard, P.; Meijer, L. Pharmacological inhibitors of cyclin-dependent kinases. Trends Pharmacol. Sci. 2002, 23, 417-425.
9. Keenan, S. M.; Welsh, W. J. Characteristics of the Plasmodium falciparum PK5 ATP-binding site: implications for the design of novel antimalarial agents. J. Mol. Graphics Modell. 2004, 22, 241-247.
10. Holton, S.; Merckx, A.; Burgess, D.; Doerig, C.; Noble, M.; et al. Structures of P. falciparum PfPK5 test the CDK regulation paradigm and suggest mechanisms of small molecule inhibition. Structure (Camb) 2003, 11, 1329-1337.
11. Woodard, C. L.; Li, Z.; Kathcart, A. K.; Terrell, J.; Gerena, L.; et al. Oxindole-based compounds are selective inhibitors of Plasmodium falciparum cyclin dependent protein kinases. J. Med. Chem 2003, 46, 3877-3882.
12. Ikuta, M.; Kamata, K.; Fukasawa, K.; Honma, T.; Machida, T.; et al. Crystallographic approach to identification of cyclin-dependent kinase 4 (CDK4)-specific inhibitors by using CDK4 mimic CDK2 protein. J. Biol. Chem. 2001, 276, 27548-27554.
13. Waters, N. C.; Geyer, J. A. Cyclin-dependent protein kinases as therapeutic drug targets for antimalarial drug development. Expert Opin. Ther. Targets 2003, 7, 7-17.
14. Doerig, C.; Endicott, J.; Chakrabarti, D. Cyclin-dependent kinase homologues of Plasmodium falciparum. Int. J. Parasitol. 2002, 32, 1575-1585.
15. Ross-Macdonald, P. B.; Graeser, R.; Kappes, B.; Franklin, R.; Williamson, D. H. Isolation and expression of a gene specifying a cdc2-like protein kinase from the human malaria parasite Plasmodium falciparum. Ear. J. Biochem. 1984, 220, 693-701.
16. Graeser, R.; Wernli, B.; Franklin, R. M.; Kappes, B. Plasmodium falciparum protein kinase 5 and the malarial nuclear division cycles. Mol. Biochem. Parasitol. 1993, 82, 37-49.
17. Harmse, L.; van Zyl, R.; Gray, N.; Schultz, P.; Leclerc, S.; et al. Structure-activity relationships and inhibitory effects of various purine derivatives on the in vitro growth of Plasmodium falciparum. Biochem. Pharmacol. 2001, 62, 341-348.
18. Li, J. L.; Robson, K. J.; Chen, J. L.; Targett, G. A.; Baker, D. A. Pfmrk, a MO15-related protein kinase from Plasmodium falciparum. Gene cloning, sequence, stage-specific expression and chromosome localization. Eur. J. Biochem. 1996, 241, 805-813.
19. Waters, N. C.; Woodard, C. L.; Prigge, S. T. Cyclin H activation and drug susceptibility of the Pfmrk cyclin dependent protein kinase from Plasmodium falciparum. Mol. Biochem. Parasitol. 2000, 107, 45-55.
20. Xiao, Z.; Waters, N. C.; Woodard, C. L.; Li, Z.; Li, P. K. Design and synthesis of Pfmrk inhibitors as potential antimalarial agents. Bioorg. Med. Chem. Lett. 2001, 11, 2875-2878.
21. CATALYST, 4.7 ed.; Accelrys: San Diego, CA.
22. Kurogi, Y.; Guner, O. F. Pharmacophore modeling and three-dimensional database searching for drug design using catalyst. Curr. Med. Chem. 2001, 8, 1035-1055.
23. Chemical Information System; Division of Experimental Therapeutics, Walter Reed Army Institute of Research, Silver Spring, MD.
24. Honma, T.; Hayashi, K.; Aoyama, T.; Hashimoto, N.; Machida, T.; et al. Structure-based generation of a new class of potent Cdk4 inhibitors: new de novo design strategy and library design. J. Med. Chem. 2001, 44, 4615-4627.
25. De Bondt, H. L.; Rosenblatt, J.; Jancarik, J.; Jones, H. D.; Morgan, D. O.; et al. Crystal structure of cyclin-dependent kinase 2. Nature 1993, 363, 595-602.
26. Hardcastle, I. R.; Golding, B. T.; Griffin, R. J. Designing inhibitors of cyclin-dependent kinases. Annu. Rev. Pharmacol. Toxicol. 2002, 42, 325-348.
27. Brown, N. R.; Noble, M. E.; Lawrie, A. M.; Morris, M. C.; Tunnah, P.; et al. Effects of phosphorylation of threonine 160 on cyclin-dependent kinase 2 structure and activity. J. Biol. Chem. 1999, 274, 8746-8756.
28. Noble, M. E.; Endicott, J. A. Chemical inhibitors of cyclin-dependent kinases: insights into design from X-ray crystallographic studies. Pharmacol. Ther. 1999, 82, 269-278.
29. De Azevedo, W. F.; Leclerc, S.; Meijer, L.; Havlicek, L.; Strnad, M.; et al. Inhibition of cyclin-dependent kinases by purine analogues: crystal structure of human cdk2 complexed with roscovitine. Eur J. Biochem. 1997, 243, 518-526.
30. De Azevedo, W. F., Jr.; Mueller-Dieckmann, H. J.; Schulze-Gahmen, U.; Worland, P. J.; Sausville, E.; et al. Structural basis for specificity and potency of a flavonoid inhibitor of human CDK2, a cell cycle kinase. Proc. Natl. Acad. Sci. U.S.A. 1996, 93, 2735-2740.
31. Honma, T.; Yoshizumi, T.; Hashimoto, N.; Hayashi, K.; Kawanishi, N.; et al. A novel approach for the development of selective Cdk4 inhibitors: library design based on locations of Cdk4 specific amino acid residues. J. Med. Chem. 2001, 44, 4628-4640.
32. Le Roch, K.; Sestier, C.; Dorin, D.; Waters, N.; Kappes, B.; et al. Activation of a Plasmodium falciparum cdc2-related kinase by heterologous p25 and cyclin H. Functional characterization of a P. falciparum cyclin homologue. J. Biol. Chem. 2000, 275, 8952-8958.
33. Gunner, O. A. Pharmacophore, perception, development, and use in drug design; University International Line: San Diego, 2000; pp 17-20.
34. Grigorov, M.; Weber, J.; Tronchet, J. M.; Jefford, C. W.; Milhous, W. K.; et al. A QSAR study of the antimalarial activity of some synthetic 1,2,4-trioxanes. J. Chem. Inf. Comput. Sci. 1997, 37, 124-130.
35. Greenidge, P. A.; Weiser, J. A comparison of methods for pharmacophore generation with the catalyst software and their use for 3D-QSAR: application to a set of 4-aminopyridine thrombin inhibitors. Mini-Rev. Med. Chem. 2001, 1, 79-87.
36. Bhattacharjee, A. K.; Kartell, M. G.; Nichols, D. A.; Hicks, R. P.; Stanton, B.; et al. Structure-activity relationship study of antimalarial indolo [2,1-b]quinazoline-6,12-diones (tryptanthrins). Three-dimensional pharmacophore modeling and identification of new antimalarial candidates. Eur. J. Med. Chem. 2004, 39, 59-67.
37. Cerius2 and Topkat; Accelrys Inc: San Diego, CA.