In silico activity profiling reveals the mechanism of action of antimalarials discovered in a high-throughput screen

Proceedings of the National Academy of Sciences of the United States of America

Volumn 105, Issue 26, 2008, Pages 9059-9064

  Plouffe, David ^a   Brinker, Achim ^a   McNamara, Case ^a   Henson, Kerstin ^a   Kato, Nobutaka ^a   Kuhen, Kelli ^a   Nagle, Advait ^a   Adrián, Francisco ^a   Matzen, Jason T ^a   Anderson, Paul ^a   Nam, Tae Gyu ^b   Gray, Nathanael S ^a,c   Chatterjee, Arnab ^a   Janes, Jeff ^a   Yan, S Frank ^a   Trager, Richard ^a   Caldwell, Jeremy S ^a   Schultz, Peter G ^a,b   Zhou, Yingyao ^a   Winzeler, Elizabeth A ^a,b  

^a GENOMICS INSTITUTE OF THE NOVARTIS RESEARCH FOUNDATION   (United States)

^b SCRIPPS RESEARCH INSTITUTE   (United States)

^c HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Antifolates; Cheminformatics; High throughput screening; Plasmodium falciparum

Indexed keywords

10 DEAZAAMINOPTERIN; ACETARSOL; ANISOMYCIN; ANTIMALARIAL AGENT; ARTEMISININ; ASTEMIZOLE; BENFLUMETOL; CHLOROQUINE; CYCLOGUANIL; EDATREXATE; EMETINE; FASCAPLYSIN; FOLIC ACID ANTAGONIST; MEFLOQUINE; MEPACRINE; MIZORIBINE; PEPSTATIN; PERHEXILINE; PRIMAQUINE; PROPAFENONE; PROTEIN SYNTHESIS INHIBITOR; PYRIMETHAMINE; QUININE; SANGIVAMYCIN; STAUROSPORINE; TONZONIUM BROMIDE; UNINDEXED DRUG; VALINOMYCIN; VERAPAMIL; VERRUCARIN A; DIHYDROFOLATE REDUCTASE;

ANTIBIOTIC RESISTANCE; ANTIMALARIAL ACTIVITY; ARTICLE; BIOCHEMISTRY; CELL PROLIFERATION; COMPUTER MODEL; DRUG IDENTIFICATION; DRUG INHIBITION; DRUG MECHANISM; ENZYME INHIBITION; ERYTHROCYTE; HIGH THROUGHPUT SCREENING; METHODOLOGY; NONHUMAN; PLASMODIUM FALCIPARUM; PREDICTION; PRIORITY JOURNAL; PROTEIN TARGETING; STRUCTURE ACTIVITY RELATION; VALIDATION PROCESS; ANIMAL; BIOLOGY; CHEMICAL STRUCTURE; CHEMISTRY; CLUSTER ANALYSIS; DRUG EFFECT; DRUG RESISTANCE; DRUG SCREENING; ENZYMOLOGY; MALARIA; PARASITE; REPRODUCIBILITY;

PLASMODIUM FALCIPARUM;

ANIMALS; ANTIMALARIALS; CLUSTER ANALYSIS; COMPUTATIONAL BIOLOGY; DRUG EVALUATION, PRECLINICAL; DRUG RESISTANCE; FOLIC ACID ANTAGONISTS; MALARIA; MODELS, MOLECULAR; PARASITES; PLASMODIUM FALCIPARUM; REPRODUCIBILITY OF RESULTS; STRUCTURE-ACTIVITY RELATIONSHIP; TETRAHYDROFOLATE DEHYDROGENASE;

EID: 48249095940     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.0802982105     Document Type: Article

References (36)

1. Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL (2007) Drugs for bad bugs: Confronting the challenges of antibacterial discovery. Nat Rev Drug Discovery 6:29-40.
2. Smilkstein M, et al. (2004) Simple and inexpensive fluorescence-based technique for high-throughput antimalarial drug screening. Antimicrob Agents Chemother 48:1803-1806.
3. Desjardins RE, Canfield CJ, Haynes JD, Chulay JD (1979) Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob Agents Chemother 16:710-718.
4. Elabbadi N, Ancelin ML, Vial HJ (1992) Use of radioactive ethanolamine incorporation into phospholipids to assess in vitro antimalarial activity by the semiautomated microdilution technique. Antimicrob Agents Chemother 36:50-55.
5. Iber PK, Pavanand K, Wilks NE, Colwell EJ (1975) Evaluation of in vitro drug sensitivity of human Plasmodium falciparum by incorporation of radioactive isoleucine. J Med Assoc Thailand 58:559-566.
6. Baniecki ML, Wirth DF, Clardy J (2007) High-throughput Plasmodium falciparum growth assay for malaria drug discovery. Antimicrob Agents Chemother 51:716-723.
7. Bennett TN, et al. (2004) Novel, rapid, and inexpensive cell-based quantification of antimalarial drug efficacy. Antimicrob Agents Chemother 48:1807-1810.
8. Druilhe P, et al. (2001) A colorimetric in vitro drug sensitivity assay for Plasmodium falciparum based on a highly sensitive double-site lactate dehydrogenase antigencapture enzyme-linked immunosorbent assay. Am J Trop Med Hyg 64:233-241.
9. Corbett Y, et al. (2004) A novel DNA-based microfluorimetric method to evaluate antimalarial drug activity. Am J Trop Med Hyg 70:119-124.
10. Johnson JD, et al. (2007) Assessment and continued validation of the malaria SYBR green I-based fluorescence assay for use in malaria drug screening. Antimicrob Agents Chemother 51:1926-1933.
11. Chanda SK, Caldwell JS (2003) Fulfilling the promise: Drug discovery in the post-genomic era. Drug Discovery Today 8:168-174.
12. Zhou Y, et al. (2007) Large-scale annotation of small-molecule libraries using public databases. J Chem Inf Model 47:1386-1394.
13. Chong CR, et al. (2006) A clinical drug library screen identifies astemizole as an antimalarial agent. Nat Chem Biol 2:415-416.
14. Weisman JL, et al. (2006) Searching for new antimalarial therapeutics amongst known drugs. Chem Biol Drug Design 67:409-416.
15. Boss C, et al. (2003) Inhibitors of the Plasmodium falciparum parasite aspartic protease plasmepsin II as potential antimalarial agents. Curr Med Chem 10:883-907.
16. Liu J, et al. (2006) Plasmodium falciparum ensures its amino acid supply with multiple acquisition pathways and redundant proteolytic enzyme systems. Proc Natl Acad Sci USA 103:8840-8845.
17. Steele JC, Warhurst DC, Kirby GC, Simmonds MS (1999) In vitro and in vivo evaluation of betulinic acid as an antimalarial. Phytother Res 13:115-119.
18. Webster HK, Whaun JM (1982) Antimalarial properties of bredinin. Prediction based on identification of differences in human host-parasite purine metabolism. J Clin Invest 70:461-469.
19. Sufrin JR, et al. (1995) Methionine recycling pathways and antimalarial drug design. Antimicrob Agents Chemother 39:2511-2515.
20. Yan SF, Asatryan H, Li J, Zhou Y (2005) Novel statistical approach for primary high-throughput screening hit selection. J Chem Inf Model 45:1784-1790.
21. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Delivery Rev 46:3-26.
22. Zhou Y, et al. (2008) Evidence-based annotation of the malaria parasite's genome using comparative expression profiling. PLoS ONE 3:e1570.
23. Weir MR, Peppler R, Gomolka D, Handwerger BS (1993) Calcium channel blockers inhibit cellular uptake of thymidine, uridine and leucine: The incorporation of these molecules into DNA, RNA and protein in the presence of calcium channel blockers is not a valid measure of lymphocyte activation. Immunopharmacology 25:75-82.
24. Brinckerhoff CE, Lubin M (1977) Prolonged inhibition of protein and glycoprotein synthesis in tumor cells treated with muconomycin A. J Natl Cancer Inst 58:605-609.
25. Cohen MB, Glazer RI (1985) Cytotoxicity and the inhibition of ribosomal RNA processing in human colon carcinoma cells. Mol Pharmacol 27:308-313.
26. Yuthavong Y, Kamchonwongpaisan S, Leartsakulpanich U, Chitnumsub P (2006) Folate metabolism as a source of molecular targets for antimalarials. Future Microbiol 1:113-125.
27. Ghose AK, Herbertz T, Salvino JM, Mallamo JP (2006) Knowledge-based chemoinformatic approaches to drug discovery. Drug Discovery Today 11:1107-1114.
28. Gregson A, Plowe CV (2005) Mechanisms of resistance of malaria parasites to antifolates. Pharmacol Rev 57:117-145.
29. Yuvaniyama J, et al. (2003) Insights into antifolate resistance from malarial DHFR-TS structures. Nat Struct Biol 10:357-365.
30. Morris GM, et al. (1998) Automated docking using a Lamarckian genetic algorithm and empirical binding free energy function. J Comput Chem 19:1639-1662.
31. Yuthavong Y, et al. (2005) Malarial (Plasmodium falciparum) dihydrofolate reductase-thymidylate synthase: Structural basis for antifolate resistance and development of effective inhibitors. Parasitology 130:249-259.
32. Elslager EF, et al. (1984) Folate antagonists. 22. Antimalarial and antibacterial effects of 2,4-diamino-6-quinazolinesulfonamides. J Med Chem 27:1740-1743.
33. Knockaert M, et al. (2000) Intracellular targets of cyclin-dependent kinase inhibitors: Identification by affinity chromatography using immobilised inhibitors. Chem Biol 7:411-422.
34. Weinstein JN, et al. (1997) An information-intensive approach to the molecular pharmacology of cancer. Science 275:343-349.
35. Giaever G, et al. (1999) Genomic profiling of drug sensitivities via induced haploinsufficiency. Nat Genet 21:278-283.
36. Hansch C, Dietrich SW, Fukunaga JY (1981) Inhibition of bovine and rat liver dihydrofolate reductase by 4,6-diamino-1,2-dihydro-2,2-dimethyl-1-(4- substituted-phenyl)-s-triazines. J Med Chem 24:544-549.