Properly substituted analogues of BIX-01294 lose inhibition of G9a histone methyltransferase and gain selective anti-DNA methyltransferase 3A activity

PLoS ONE

Volumn 9, Issue 5, 2014, Pages

  Rotili, Dante ^a   Tarantino, Domenico ^a   Marrocco, Biagina ^a   Gros, Christina ^b   Masson, Véronique ^b   Poughon, Valérie ^b   Ausseil, Fréderic ^b   Chang, Yanqi ^c   Labella, Donatella ^a   Cosconati, Sandro ^d   Di Maro, Salvatore ^e   Novellino, Ettore ^e   Schnekenburger, Michael ^f   Grandjenette, Cindy ^f   Bouvy, Celine ^f   Diederich, Marc ^f,g   Cheng, Xiaodong ^c   Arimondo, Paola B ^b   Mai, Antonello ^a  

^a SAPIENZA UNIVERSITY OF ROME   (Italy)

^b INSTITUT DE RECHERCHE PIERRE FABRE   (France)

^c EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d SECOND UNIVERSITY OF NAPLES   (Italy)

^e UNIVERSITY OF NAPLES FEDERICO II   (Italy)

^f Laboratoire de Biologie Molé Culaire et Cellulaire du Cancer LBMCC   (Luxembourg)

^g Seoul National University   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

4 (1 BENZYLPIPERIDIN 4 YL) 2 (CYCLO ALKYLAMINO)QUINAZOLIN 4 AMINE DERIVATIVE; DNA METHYLTRANSFERASE 1; DNA METHYLTRANSFERASE 3A; DNA METHYLTRANSFERASE INHIBITOR; HISTONE H3 LYSINE 9 METHYLTRANSFERASE; HISTONE METHYLTRANSFERASE; N (1 BENZYL 4 PIPERIDINYL) 2 (HEXAHYDRO 4 METHYL 1H 1,4 DIAZEPIN 1 YL) 6,7 DIMETHOXY 4 QUINAZOLINAMINE; N (1 BENZYLPIPERIDIN 4 YL) 2 (PYRROLIDIN 1 YL)QUINAZOLIN 4 AMINE; N (1 BENZYLPIPERIDIN 4 YL) 2 CHLORO QUINAZOLIN 4 AMINE; N (1 BENZYLPIPERIDIN 4 YL) 2 MORPHOLINOQUINAZOLIN 4 AMINE; SGI 1027; SINEFUNGIN; UNCLASSIFIED DRUG; AZEPINE DERIVATIVE; DNA (CYTOSINE 5) METHYLTRANSFERASE; EHMT2 PROTEIN, HUMAN; ENZYME INHIBITOR; HISTOCOMPATIBILITY ANTIGEN; HISTONE LYSINE METHYLTRANSFERASE; QUINAZOLINE DERIVATIVE;

ANTIPROLIFERATIVE ACTIVITY; ARTICLE; BINDING SITE; CELL DEATH; CELL PROLIFERATION; CELL VIABILITY; DOSE RESPONSE; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME INHIBITION; IC 50; MOLECULAR DOCKING; NUCLEOTIDE SEQUENCE; ANTAGONISTS AND INHIBITORS; CELL SURVIVAL; CHEMISTRY; DRUG EFFECTS; HUMAN; METABOLISM; STRUCTURE ACTIVITY RELATION; TUMOR CELL LINE;

AZEPINES; CATALYTIC DOMAIN; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; DNA (CYTOSINE-5-)-METHYLTRANSFERASE; ENZYME INHIBITORS; HISTOCOMPATIBILITY ANTIGENS; HISTONE-LYSINE N-METHYLTRANSFERASE; HUMANS; MOLECULAR DOCKING SIMULATION; QUINAZOLINES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84901487126     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0096941     Document Type: Article

References (29)

1. You JS, Jones PA (2012) Cancer genetics and epigenetics: two sides of the same coin? Cancer Cell 22: 9-20.
2. Mai A, Altucci L (2009) Epi-drugs to fight cancer: from chemistry to cancer treatment, the road ahead. Int J Biochem Cell Biol 41: 199-213.
3. Mai A (2010) Small-molecule chromatin-modifying agents: therapeutic applications. Epigenomics 2: 307-324.
4. Seidel C, Florean C, Schnekenburger M, Dicato M, Diederich M (2012) Chromatin-modifying agents in anti-cancer therapy. Biochimie 94: 2264-2279.
5. Florean C, Schnekenburger M, Grandjenette C, Dicato M, Diederich M (2011) Epigenomics of leukemia: from mechanisms to therapeutic applications. Epigenomics 3: 581-609.
6. Gros C, Fahy J, Halby L, Dufau I, Erdmann A, et al. (2012) DNA methylation inhibitors in cancer: recent and future approaches. Biochimie 94: 2280-2296.
7. Jia D, Jurkowska RZ, Zhang X, Jeltsch A, Cheng X (2007) Structure of Dnmt3a bound to Dnmt3L suggests a model for de novo DNA methylation. Nature 449: 248-251. (Pubitemid 47402375)
8. Mai A, Valente S, Cheng D, Perrone A, Ragno R, et al. (2007) Synthesis and biological validation of novel synthetic histone/protein methyltransferase inhibitors. ChemMedChem 2: 987-991.
9. Ragno R, Simeoni S, Castellano S, Vicidomini C, Mai A, et al. (2007) Small molecule inhibitors of histone arginine methyltransferases: homology modeling, molecular docking, binding mode analysis, and biological evaluations. J Med Chem 50: 1241-1253. (Pubitemid 46496324)
10. Mai A, Cheng D, Bedford MT, Valente S, Nebbioso A, et al. (2008) Epigenetic multiple ligands: mixed histone/protein methyltransferase, acetyltransferase, and class III deacetylase (sirtuin) inhibitors. J Med Chem 51: 2279-2290. (Pubitemid 351503283)
11. Castellano S, Milite C, Ragno R, Simeoni S, Mai A, et al. (2010) Design, synthesis and biological evaluation of carboxy analogues of arginine methyl-transferase inhibitor 1 (AMI-1). ChemMedChem 5: (3) 398-414.
12. Cheng D, Valente S, Castellano S, Sbardella G, Di Santo R, et al. (2011) Novel 3,5-bis(bromohydroxybenzylidene)piperidin-4-ones as coactivator-associated arginine methyltransferase 1 inhibitors: enzyme selectivity and cellular activity. J Med Chem 54: 4928-4932.
13. Valente S, Lepore I, Dell'Aversana C, Tardugno M, Castellano S, et al. (2012) Identification of PR-SET7 and EZH2 selective inhibitors inducing cell death in human leukemia U937 cells. Biochimie 94: 2308-2313.
14. Kubicek S, O'Sullivan RJ, August EM, Hickey ER, Zhang Q, et al. (2007) Reversal of H3K9me2 by a small-molecule inhibitor for the G9a histone methyltransferase. Mol Cell 25: 473-481. (Pubitemid 46206139)
15. Chang Y, Ganesh T, Horton JR, Spannhoff A, Liu J, et al. (2010) Adding a lysine mimic in the design of potent inhibitors of histone lysine methyltransferases. J Mol Biol 400: 1-7.
16. Chang Y, Zhang X, Horton JR, Upadhyay AK, Spannhoff A, et al. (2009) Structural basis for G9a-like protein lysine methyltransferase inhibition by BIX-01294. Nat Struct Mol Biol 16: 312-317.
17. Upadhyay AK, Rotili D, Han JW, Hu R, Chang Y, et al. (2012) An analog of BIX-01294 selectively inhibits a family of histone H3 lysine 9 Jumonji demethylases. J Mol Biol 416: 319-327.
18. Vedadi M, Barsyte-Lovejoy D, Liu F, Rival-Gervier S, Allali-Hassani A, et al. (2011) A chemical probe selectively inhibits G9a and GLP methyltransferase activity in cells. Nat Chem Biol 7: 566-574.
19. Ceccaldi A, Rajavelu A, Ragozin S, Senamaud-Beaufort C, Bashtrykov P, et al. (2013) Identification of Novel Inhibitors of DNA Methylation by Screening of a Chemical Library. ACS Chem Biol 8: 543-548.
20. Lee BH, Yegnasubramanian S, Lin X, Nelson WG (2005) Procainamide is a specific inhibitor of DNA methyltransferase 1. J Biol Chem 280: 40749-40756. (Pubitemid 41780565)
21. Gros C, Chauvigné L, Poulet A, Menon Y, Ausseil F, et al. (2013) Development of a universal radioactive DNA methyltransferase inhibition test for highthroughput screening and mechanistic studies. Nucleic Acids Research, 41: e185.
22. Ceccaldi A, Rajavelu A, Champion C, Rampon C, Jurkowska R, et al. (2011) C5-DNA methyltransferase inhibitors: from screening to effects on zebrafish embryo development. ChemBioChem 12: 1337-1345.
23. Epik, version 2.0 (2009) Schrödinger, LLC: New York, NY.
24. Glide; Schrödinger, LLC (2008) New York, NY.
25. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM (2004) UCSF Chimera-a visualization system for exploratory research and analysis. J Comput Chem 25: 1605-1612.
26. DeRuiter J, Brubaker AN, Millen J, Riley TN (1986) Design and synthesis of 2-(arylamino)-4(3H)-quinazolinones as novel inhibitors of rat lens aldose reductase. J Med Chem 29: 627-629. (Pubitemid 16034666)
27. Datta J, Ghoshal K, Denny WA, Gamage SA, Brooke DG, et al. (2009) A new class of quinoline-based DNA hypomethylating agents reactivates tumor suppressor genes by blocking DNA methyltransferase 1 activity and inducing its degradation. Cancer Res 69: 4277-4285.
28. Valente S, Liu Y, Schnekenburger M, Zwergel C, Cosconati S, et al. (2014) Selective Non-nucleoside Inhibitors of Human DNA Methyltransferases Active in Cancer Including in Cancer Stem Cells. J Med Chem 57: 701-713.
29. Yoo J, Choi S, Medina-Franco JL (2013) Molecular modeling studies of the novel inhibitors of DNA methyltransferases SGI-1027 and CBC12: implications for the mechanism of inhibition of DNMTs. PloS One 8: e62152.