Natural products as DNA methyltransferase inhibitors: A computer-aided discovery approach

Molecular Diversity

Volumn 15, Issue 2, 2011, Pages 293-304

  Medina Franco, Jose L ^a   López Vallejo, Fabian ^a   Kuck, Dirk ^b   Lyko, Frank ^b  

^a TORREY PINES INSTITUTE FOR MOLECULAR STUDIES   (United States)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

Author keywords

Cancer; Curcumin; DNA methylation; Drug discovery; EGCG; Natural product database; Virtual screening

Indexed keywords

CURCUMIN; DNA METHYLTRANSFERASE 1; DNA METHYLTRANSFERASE INHIBITOR; EPIGALLOCATECHIN GALLATE; NATURAL PRODUCT; BIOLOGICAL PRODUCT; CATECHIN; DNA (CYTOSINE 5 ) METHYLTRANSFERASE 1; DNA (CYTOSINE 5) METHYLTRANSFERASE; DNA (CYTOSINE-5-)-METHYLTRANSFERASE 1; DRUG DERIVATIVE; ENZYME INHIBITOR;

ARTICLE; BINDING AFFINITY; COMPUTER MODEL; DNA METHYLATION; DRUG ACTIVITY; DRUG PROTEIN BINDING; DRUG SCREENING; ENZYME ACTIVE SITE; IC 50; PRIORITY JOURNAL; BIOLOGY; CELL STRAIN HCT116; CELL STRAIN HEK293; CELL STRAIN HL 60; CHEMICAL STRUCTURE; CHEMISTRY; COMPUTER INTERFACE; COMPUTER SIMULATION; DRUG ANTAGONISM; DRUG DESIGN; DRUG EFFECT; HUMAN; METABOLISM;

BIOLOGICAL PRODUCTS; CATECHIN; COMPUTATIONAL BIOLOGY; COMPUTER SIMULATION; CURCUMIN; DNA (CYTOSINE-5-)-METHYLTRANSFERASE; DNA METHYLATION; DRUG DESIGN; ENZYME INHIBITORS; HCT116 CELLS; HEK293 CELLS; HL-60 CELLS; HUMANS; MODELS, MOLECULAR; USER-COMPUTER INTERFACE;

EID: 79958002242     PISSN: 13811991     EISSN: 1573501X     Source Type: Journal    
DOI: 10.1007/s11030-010-9262-5     Document Type: Article

References (73)

1. Goll MG, Bestor TH (2005) Eukaryotic cytosine methyltransferases. Annu Rev Biochem 74:481-514. doi:10.1146/annurev. biochem.74.010904.153721 (Pubitemid 40995515)
2. Jones PA, Baylin SB (2007) The epigenomics of cancer. Cell 128:683-692. doi:10.1016/j.cell.2007.01.029 (Pubitemid 46273572)
3. Lyko F, Brown R (2005) DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J Natl Cancer Inst 97:1498-1506. doi:10.1093/jnci/dji311 (Pubitemid 41631949)
4. Brueckner B, Kuck D, Lyko F (2007) DNA methyltransferase inhibitors for cancer therapy. Cancer J 13:17-22. doi:10.1097/PPO. 0b013e31803c7245
5. Santi DV, Garrett CE, Barr PJ (1983) On the mechanism of inhibition of DNA cytosine methyltransferases by cytosine analogs. Cell 33:9-10. doi:10.1016/0092-8674 (83) 90327-6 (Pubitemid 13096428)
6. Wu JC, Santi DV (1987) Kinetic and catalytic mechanism of HhaI methyltransferase. J Biol Chem 262:4778-4786 (Pubitemid 17102852)
7. Chen L, Macmillan AM, Chang W, Ezaznikpay K, Lane WS, Verdine GL (1991) Direct identification of the active-site nucleophile in a DNA (cytosine-5)-methyltransferase. Biochemistry 30:11018-11025. doi:10.1021/bi00110a002
8. Ogara M, Klimasauskas S, Roberts RJ, Cheng XD (1996) Enzymatic C5-cytosine methylation of DNA: mechanistic implications of new crystal structures for H haI methyltransferase-DNA-Ado-Hcy complexes. J Mol Biol 261:634-645. doi:10.1006/jmbi.1996. 0489 (Pubitemid 26300798)
9. Kumar S, Horton JR, Jones GD, Walker RT, Roberts RJ, Cheng X (1997) DNA containing 4'-thio-2'-deoxycytidine inhibits methylation by HhaI methyltransferase. Nucleic Acids Res 25:2773-2783. doi:10.1093/nar/25.14.2773 (Pubitemid 27299791)
10. Jurkowski TP, Meusburger M, Phalke S, Helm M, Nellen W, Reuter G, Jeltsch A (2008) Human DNMT2 methylates tRNA (Asp) molecules using a DNA methyltransferase-like catalytic mechanism. RNA 14:1663-1670. doi:10.1261/rna.970408
11. Suzuki T, Miyata N (2006) Epigenetic control using natural products and synthetic molecules. Curr Med Chem 13:935-958. doi:10. 2174/092986706776361067
12. Liu K, Wang YF, Cantemir C, Muller MT (2003) Endogenous assays of DNA methyltransferases: evidence for differential activities of DNMT1, DNMT2, and DNMT3 inmammalian cellsinvivo. Mol Cell Biol 23:2709-2719. doi:10.1128/mcb.23.8. 2709-2719. 2003 (Pubitemid 36403072)
13. Stresemann C, Lyko F (2008) Modes of action of the DNA methyltransferase inhibitors azacytidine and decitabine. Int J Cancer 123:8-13. doi:10.1002/ijc.23607 (Pubitemid 351705186)
14. Schermelleh L, Spada F, Easwaran HP, Zolghadr K, Margot JB, Cardoso MC, Leonhardt H (2005) Trapped in action: direct visualization of DNA methyltransferase activity in living cells. Nat Methods 2:751-756. doi:10.1038/nmeth794 (Pubitemid 41486206)
15. Segura-Pacheco B, Trejo-Becerril C, Perez-Cardenas E, Taja-Chayeb L, Mariscal I, Chavez A, Acuna C, Salazar AM, Lizano M, Duenas-Gonzalez A (2003) Reactivation of tumor suppressor genes by the cardiovascular drugs hydralazine and procainamide and their potential use in cancer therapy. Clin Cancer Res 9:1596-1603 (Pubitemid 36554581)
16. Segura-Pacheco B, Perez-Cardenas E, Taja-Chayeb L, Chavez-Blanco A, Revilla-Vazquez A, Benitez-Bribiesca L, Duenas-Gonzalez A (2006) Global DNA hypermethylation-associated cancer chemotherapy resistance and its reversion with the demethylating agent hydralazine. J Transl Med 4:32. doi:10.1186/1479-5876-4-32 (Pubitemid 44437729)
17. Villar-Garea A, Fraga MF, Espada J, Esteller M (2003) Procaine is a DNA-demethylating agent with growth-inhibitory effects in human cancer cells. Cancer Res 63:4984-4989 (Pubitemid 37022635)
18. Lee BH, Yegnasubramanian S, Lin XH, Nelson WG (2005) Procainamide is a specific inhibitor of DNA methyltransferase 1. J Biol Chem 280:40749-40756. doi:10.1074/jbc. M505593200 (Pubitemid 41780565)
19. Castellano S, Kuck D, Sala M, Novellino E, Lyko F, Sbardella G (2008) Constrained analogues of procaine as novel small molecule inhibitors of DNA methyltransferase-1. J Med Chem 51:2321-2325. doi:10.1021/jm7015705 (Pubitemid 351503289)
20. Siedlecki P, Boy RG, Musch T, Brueckner B, Suhai S, Lyko F, Zielenkiewicz P (2006) Discovery of two novel, small-molecule inhibitors of DNA methylation. J Med Chem 49:678-683. doi:10. 1021/jm050844z (Pubitemid 43157497)
21. Kuck D, Singh N, Lyko F, Medina-Franco JL (2010) Novel and selective DNA methyltransferase inhibitors: docking-based virtual screening and experimental evaluation. Bioorg Med Chem 18:822-829. doi: 10.1016/j.bmc.2009.11.050
22. Harvey AL (2008) Natural products in drug discovery. Drug Discov Today 13:894-901. doi:10.1016/j.drudis.2008.07.004
23. Ganesan A (2008) The impact of natural products upon modern drug discovery. Curr Opin Chem Biol 12:306-317. doi:10.1016/j. cbpa.2008.03.016
24. Butler MS (2008) Natural products to drugs: natural productderived compounds in clinical trials. Nat Prod Rep 25:475-516. doi:10.1039/b514294f (Pubitemid 351725315)
25. Newman DJ (2008) Natural products as leads to potential drugs: an old process or the new hope for drug discovery?. J Med Chem 51:2589-2599. doi: 10.1021/jm0704090 (Pubitemid 351620778)
26. Molinski TF, Dalisay DS, Lievens SL, Saludes JP (2009) Drug development from marine natural products. Nat Rev Drug Discov 8:69-85. doi:10.1038/nrd2487
27. Demain AL, Sanchez S (2009) Microbial drug discovery: 80 years of progress. J Antibiot 62:5-16. doi:10.1038/ja.2008.16
28. Cragg GM, Newman DJ (2009) Nature: a vital source of leads for anticancer drug development. Phytochem Rev 8:313-331. doi: 10. 1007/s11101-009-9123-y
29. Coseri S (2009) Natural products and their analogues as efficient anticancer drugs. Mini-Rev Med Chem 9:560-571. doi:10.2174/138955709788167592
30. Kinghorn AD, Chin YW, Swanson SM (2009) Discovery of natural product anticancer agents from biodiverse organisms. Curr Opin Drug Discov Dev 12:189-196
31. Hauser AT, Jung M (2008) Targeting epigenetic mechanisms: potential of natural products in cancer chemoprevention. Planta Med 74:1593-1601. doi:10.1055/s-2008-1081347
32. Yu N, Wang M (2008) Anticancer drug discovery targeting DNA hypermethylation. Curr Med Chem 15:1350-1375. doi: 10.2174/092986708784567653 (Pubitemid 351997787)
33. Fang MZ, Wang YM, Ai N, Hou Z, Sun Y, Lu H, Welsh W, Yang CS (2003) Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines. Cancer Res 63:7563-7570 (Pubitemid 37466673)
34. Lee WJ, Shim JY, Zhu BT (2005) Mechanisms for the inhibition of DNA methyltransferases by tea catechins and bioflavonoids. Mol Pharmacol 68:1018-1030. doi: 10.1124/mol.104.008367 (Pubitemid 41345793)
35. Lee WJ, Zhu BT (2006) Inhibition of DNA methylation by caffeic acid and chlorogenic acid, two common catechol-containing coffee polyphenols. Carcinogenesis 27:269-277. doi:10.1093/carcin/bgi206 (Pubitemid 43159879)
36. Fini L, Selgrad M, Fogliano V, Graziani G, Romano M, Hotchkiss E, Daoud YA, De Vol EB, Boland CR, Ricciardiello L (2007) Annurca apple polyphenols have potent demethylating activity and can reactivate silenced tumor suppressor genes in colorectal cancer cells. J Nutr 137:2622-2628. doi:10.3945/jn. 109.118521 (Pubitemid 350255288)
37. Fang MZ, Chen DP, Sun Y, Jin Z, Christman JK, Yang CS (2005) Reversal of hypermethylation and reactivation of p16INK4a, RARß, and MGMT genes by genistein and other isoflavones from soy. Clin Cancer Res 11:7033-7041. doi:10.1158/1078-0432.ccr-05-0406 (Pubitemid 41428763)
38. Jagadeesh S, Sinha S, Pal BC, Bhattacharya S, Banerjee PP (2007) Mahanine reverses an epigenetically silenced tumor suppressor gene RASSF1A in human prostate cancer cells. Biochem Biophys Res Commun 362:212-217. doi:10.1016/j.bbrc. 2007.08.005 (Pubitemid 47296313)
39. Pina IC, Gautschi JT, Wang GYS, Sanders ML, Schmitz FJ, France D, Cornell-Kennon S, Sambucetti LC, Remiszewski SW, Perez LB, Bair KW, Crews P (2003) Psammaplins from the sponge Pseudoceratina purpurea: inhibition of both histone deacetylase and DNA methyltransferase. J Org Chem 68:3866-3873. doi:10. 1021/jo034248t (Pubitemid 36576636)
40. McPhail KL, France D, Cornell-Kennon S, Gerwick WH (2004) Peyssonenynes A and B, novel enediyne oxylipins with DNA methyl transferase inhibitory activity from the red marine alga Peyssonnelia caulifera. J Nat Prod 67:1010-1013. doi:10.1021/np0400252 (Pubitemid 38823335)
41. Liu ZF, Liu SJ, Xie ZL, Pavlovicz RE, Wu J, Chen P, Aimiuwu J, Pang JX, Bhasin D, Neviani P, Fuchs JR, Plass C, Li PK, Li C, Huang THM, Wu LC, Rush L, Wang HY, Perrotti D, Marcucci G, Chan KK (2009) Modulation of DNA methylation by a sesquiterpene lactone parthenolide. J Pharmacol Exp Ther 329:505-514. doi:10.1124/jpet.108.147934
42. Liu ZF, Xie ZL, Jones W, Pavlovicz RE, Liu SJ, Yu JH, Li PK, Lin JY, Fuchs JR, Marcucci G, Li CL, Chan KK (2009) Curcumin is a potent DNA hypomethylation agent. Bioorg Med Chem Lett 19:706-709. doi:10.1016/j.bmcl.2008. 12.041
43. Singh N, Dueñas-González A, Lyko F, Medina-Franco JL (2009) Molecular modeling and dynamics studies of hydralazine with human DNA methyltransferase 1. ChemMedChem 4:792-799. doi:10.1002/cmdc.200900017
44. Siedlecki P, Boy RG, Comagic S, Schirrmacher R, Wiessler M, Zielenkiewicz P, Suhai S, Lyko F (2003) Establishment and functional validation of a structural homology model for human DNA methyltransferase 1. Biochem Biophys Res Commun 306:558-563. doi:10.1016/s0006-291x (03) 01000-3 (Pubitemid 36683111)
45. Brueckner B, Boy RG, Siedlecki P, Musch T, Kliem HC, Zielenkiewicz P, Suhai S, Wiessler M, Lyko F (2005) Epigenetic reactivation of tumor suppressor genes by a novel small-molecule inhibitor of human DNA methyltransferases. Cancer Res 65:6305-6311. doi:10.1158/0008-5472. CAN-04-2957 (Pubitemid 40994416)
46. Stach D, Schmitz OJ, Stilgenbauer S, Benner A, Dohner H, Wiessler M, Lyko F (2003) Capillary electrophoretic analysisofgenomic DNA methylation levels. Nucleic Acids Res 31:e2. doi:10.1093/nar/gng002
47. Irwin JJ, Shoichet BK (2005) ZINC-a free database of commercially available compounds for virtual screening. J Chem Inf Model 45:177-182. doi:10.1021/ci049714+ (Pubitemid 40736970)
48. FILTER, version 2.0.2. OpenEye Scientific Software Inc., Santa Fe, NM. http://www.eyesopen.com. Accessed April 2010)
49. LigPrep, version 2.2 (2005) Schrödinger, LLC, New York, NY
50. Xu Y, Johnson M (2001) Algorithm for naming molecular equivalence classes represented by labeled pseudographs. J Chem Inf Comput Sci 41:181-185. doi:10.1021/ci0003911 (Pubitemid 33645688)
51. Xu YJ, Johnson M (2002) Using molecular equivalence numbers to visually explore structural features that distinguish chemical libraries. J Chem Inf Comput Sci 42:912-926. doi:10.1021/ci025535l (Pubitemid 35355241)
52. Xu J (2002) A new approach to finding natural chemical structure classes. J Med Chem 45:5311-5320. doi:10.1021/jm010520k (Pubitemid 35429170)
53. Liu B, Lu A, Zhang L, Liu H, Liu Z, Zhou J (2004) New diversity criterion and database compression method. Internet Electron J Mol Des 3:143-149. http://www.biochempress.com
54. Bemis GW, Murcko MA (1996) The properties of known drugs. 1. Molecular frameworks. J Med Chem 39:2887-2893. doi:10. 1021/jm9602928 (Pubitemid 26251026)
55. Medina-Franco JL, Petit J, Maggiora GM (2006) Hierarchical strategy for identifying active chemotype classes in compound databases. Chem Biol Drug Des 67:395-408. doi:10.1111/j. 1747-0285.2006.00397.x (Pubitemid 44086976)
56. Medina-Franco JL, Martinez-Mayorga K, Giulianotti MA, Houghten RA, Pinilla C (2008) Visualization of the chemical space in drug discovery. Curr Comput Aided Drug Des 4:322-333. doi:10. 2174/157340908786786010
57. Singh N, Guha R, Giulianotti MA, Pinilla C, Houghten RA, Medina-Franco JL (2009) Chemoinformatic analysis of combinatorial libraries, drugs, natural products, and molecular libraries small molecule repository. J Chem Inf Model 49:1010-1024. doi:10.1021/ci800426u
58. Medina-Franco JL, Martínez-Mayorga K, Bender A, Scior T (2009) Scaffold diversity analysis of compound data sets using an entropy-based measure. QSAR Comb Sci 28:1551-1560. doi:10. 1002/qsar.200960069
59. Molecular Operating Environment (MOE), version 2008.10. Chemical Computing Group Inc., Montreal, QC, Canada. http://www.chemcomp.com. Accessed April 2010
60. Glide, version 5.0 (2008) Schrödinger, LLC, New York, NY
61. Jones G, Willett P, Glen RC, Leach AR, Taylor R (1997) Development and validation of a genetic algorithm for flexible docking. J Mol Biol 267:727-748. doi:10.1006/jmbi.1996.0897 (Pubitemid 27170693)
62. Huey R, Morris GM, Olson AJ, Goodsell DS (2007) A semiempirical free energy force field with charge-based desolvation. J Comput Chem 28:1145-1152. doi:10.1002/jcc.20634 (Pubitemid 46506716)
63. Morris GM, Huey R, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, Olson AJ (2009) AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem 30:2785-2791. doi:10.1002/jcc.21256
64. Gasteiger J, Marsili M (1980) Iterative partial equalization of orbital electronegativity-a rapid access to atomic charges. Tetrahedron 36:3219-3228. doi:10.1016/0040-4020 (80) 80168-2
65. Chuang JC, Yoo CB, Kwan JM, Li TWH, Liang GN, Yang AS, Jones PA (2005) Comparison of biological effects of nonnucleoside DNA methylation inhibitors versus 5-aza-2'-deoxycytidine. Mol Cancer Ther 4:1515-1520. doi:10.1158/1535- 7163. MCT-05-0172 (Pubitemid 41556433)
66. Stresemann C, Brueckner B, Musch T, Stopper H, Lyko F (2006) Functional diversity of DNA methyltransferase inhibitors in human cancer cell lines. Cancer Res 66:2794-2800. doi:10. 1158/0008-5472. CAN-05-2821
67. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M (2008) DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res 36:D901-D-D906. doi:10.1093/nar/gkm958 (Pubitemid 351149842)
68. Charifson PS, Walters WP (2002) Filtering databases and chemical libraries. J Comput Aided Mol Des 16:311-323. doi:10.1023/A:1020829519597 (Pubitemid 35414665)
69. Talevi A, Gavernet L, Bruno-Blanch LE (2009) Combined virtual screening strategies. Curr Comput Aided Drug Des 5:23-37. doi:10.2174/157340909787580854
70. Musa MA, Cooperwood JS, Khan MOF (2008) A review of coumarin derivatives in pharmacotherapy of breast cancer. Curr Med Chem 15:2664-2679
71. Wu L, Wang X, Xu W, Farzaneh F, Xu R (2009) The structure and pharmacological functions of coumarins and their derivatives. Curr Med Chem 16:4236-4260. doi:10.2174/092986709789578187
72. CRC Dictionary of Natural Products. http://www.crcpress.com/. Accessed April 2010
73. Drug Discovery Portal. http://www.ddp.strath.ac.uk/. Accessed April 2010