Discovery of a potent small molecule SIRT1/2 inhibitor with anticancer effects

International Journal of Oncology

Volumn 43, Issue 4, 2013, Pages 1205-1211

  Choi, Gildon ^a   Lee, Jongkook ^b   Ji, Jeong Yeon ^b   Woo, Jimin ^a   Kang, Nam Sook ^c   Cho, Sung Yun ^a   Kim, Hyoung Rae ^a   Ha, Jae Du ^a   Han, Sun Young ^b  

^a University of Science and Technology (UST)   (South Korea)

^b Gyeongsang National University   (South Korea)

^c Chungnam National University   (South Korea)

Author keywords

Anticancer agent; SIRT1; SIRT2; Toxoflavin

Indexed keywords

ALPHA TUBULIN; ANTINEOPLASTIC AGENT; ENZYME INHIBITOR; PROTEIN P53; SIRTUIN 1; SIRTUIN 2; UNCLASSIFIED DRUG; XANTHOTHRICIN;

ACETYLATION; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; CELL GROWTH; CONTROLLED STUDY; CYTOTOXICITY; DOSE RESPONSE; DRUG PROTEIN BINDING; ENZYME INHIBITION; GROWTH INHIBITION; PRIORITY JOURNAL; STRUCTURE ACTIVITY RELATION;

ACETYLATION; ANTINEOPLASTIC AGENTS; BENZAMIDES; CELL LINE, TUMOR; HUMANS; NEOPLASMS; PYRIMIDINONES; SIRTUIN 1; SIRTUIN 2; SMALL MOLECULE LIBRARIES; STRUCTURE-ACTIVITY RELATIONSHIP; TRIAZINES; TUBULIN;

EID: 84882436703     PISSN: 10196439     EISSN: 17912423     Source Type: Journal    
DOI: 10.3892/ijo.2013.2035     Document Type: Article

References (34)

1. Bosch-Presegue L and Vaquero A: The dual role of sirtuins in cancer. Genes Cancer 2: 648-662, 2011.
2. Carafa V, Nebbioso A and Altucci L: Sirtuins and disease: the road ahead. Front Pharmacol 3: 4, 2012.
3. North BJ, Marshall BL, Borra MT, Denu JM and Verdin E: The human Sir2 ortholog, SIRT2, is an NAD+-dependent tubulin deacetylase. Mol Cell 11: 437-444, 2003.
4. Vaquero A, Scher MB, Lee DH, et al: SirT2 is a histone deacetylase with preference for histone H4 Lys 16 during mitosis. Genes Dev 20: 1256-1261, 2006.
5. Stunkel W and Campbell RM: Sirtuin 1 (SIRT1): the misunderstood HDAC. J Biomol Screen 16: 1153-1169, 2011.
6. Bonezzi K, Belotti D, North BJ, et al: Inhibition of SIRT2 potentiates the anti-motility activity of taxanes: implications for antineoplastic combination therapies. Neoplasia 14: 846-854, 2012.
7. Napper AD, Hixon J, McDonagh T, et al: Discovery of indoles as potent and selective inhibitors of the deacetylase SIRT1. J Med Chem 48: 8045-8054, 2005.
8. Bedalov A, Gatbonton T, Irvine WP, Gottschling DE and Simon JA: Identification of a small molecule inhibitor of Sir2p. Proc Natl Acad Sci USA 98: 15113-15118, 2001.
9. Mai A, Massa S, Lavu S, et al: Design, synthesis, and biological evaluation of sirtinol analogues as class III histone/protein deacetylase (Sirtuin) inhibitors. J Med Chem 48: 7789-7795, 2005.
10. Heltweg B, Gatbonton T, Schuler AD, et al: Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes. Cancer Res 66: 4368-4377, 2006.
11. Outeiro TF, Kontopoulos E, Altmann SM, et al: Sirtuin 2 inhibitors rescue alpha-synuclein-mediated toxicity in models of Parkinson's disease. Science 317: 516-519, 2007.
12. Trapp J, Meier R, Hongwiset D, Kassack MU, Sippl W and Jung M: Structure-activity studies on suramin analogues as inhibitors of NAD+-dependent histone deacetylases (sirtuins). ChemMedChem 2: 1419-1431, 2007.
13. Lain S, Hollick JJ, Campbell J, et al: Discovery, in vivo activity, and mechanism of action of a small-molecule p53 activator. Cancer Cell 13: 454-463, 2008.
14. Lara E, Mai A, Calvanese V, et al: Salermide, a Sirtuin inhibitor with a strong cancer-specific proapoptotic effect. Oncogene 28: 781-791, 2009.
15. Kalle AM, Mallika A, Badiger J, Alinakhi, Talukdar P and Sachchidanand: Inhibition of SIRT1 by a small molecule induces apoptosis in breast cancer cells. Biochem Biophys Res Commun 401: 13-19, 2010.
16. Nebbioso A, Pereira R, Khanwalkar H, et al: Death receptor pathway activation and increase of ROS production by the triple epigenetic inhibitor UVI5008. Mol Cancer Ther 10: 2394-2404, 2011.
17. Zhang Q, Zeng SX, Zhang Y, et al: A small molecule Inauhzin inhibits SIRT1 activity and suppresses tumour growth through activation of p53. EMBO Mol Med 4: 298-312, 2012.
18. Machlowitz RA, Fisher WP, Betsey McKay S, Tytell AA and Charney J: Xanthothricin, a new antibiotic. Antibiot Chemother 4: 259-261, 1954.
19. Black TH: An improved, large-scale synthesis of xanthothricin and reumycin. J Heterocyclic Chem 24: 1373-1375, 1987.
20. Spinks D, Shanks EJ, Cleghorn LA, et al: Investigation of trypanothione reductase as a drug target in Trypanosoma brucei. ChemMedChem 4: 2060-2069, 2009.
21. Todorovic N, Giacomelli A, Hassell JA, Frampton CS and Capretta A: Microwave-assisted synthesis of 3-aryl-pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H) -dione libraries: derivatives of toxoflavin. Tetrahedron Lett 51: 6037-6040, 2010.
22. Peck B, Chen CY, Ho KK, et al: SIRT inhibitors induce cell death and p53 acetylation through targeting both SIRT1 and SIRT2. Mol Cancer Ther 9: 844-855, 2010.
23. Lu X, Magrane G, Yin C, Louis DN, Gray J and Van Dyke T: Selective inactivation of p53 facilitates mouse epithelial tumor progression without chromosomal instability. Mol Cell Biol 21: 6017-6030, 2001.
24. Vaziri H, Dessain SK, Ng Eaton E, et al: hSIR2(SIRT1) functions as an NAD-dependent p53 deacetylase. Cell 107: 149-159, 2001.
25. Venkatachalam CM, Jiang X, Oldfield T and Waldman M: LigandFit: a novel method for the shape-directed rapid docking of ligands to protein active sites. J Mol Graph Model 21: 289-307, 2003.
26. Finnin MS, Donigian JR and Pavletich NP: Structure of the histone deacetylase SIRT2. Nat Struct Biol 8: 621-625, 2001.
27. Wu S, Skolnick J and Zhang Y: Ab initio modeling of small proteins by iterative TASSER simulations. BMC Biol 5: 17, 2007.
28. Brooks BR, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S and Karplus M: CHARMM: A program for macromolecular energy, minimization, and dynamics calculations. J Comput Chem 4: 187-217, 1983.
29. Song S-H, Lee M-O, Lee J-S, Oh J-S, Cho S-U and Cha H-J: Sirt1 promotes DNA damage repair and cellular survival. Biomol Ther 19: 282-287, 2011.
30. van Veen AG and Mertens WK: Das Toxoflavin, der gelbe Giftstoff der Bongkrek. Rec Trav Chim 53: 398-404, 1934.
31. Latuasan HE and Berends W: On the origin of the toxicity of toxoflavin. Biochim Biophys Acta 52: 502-508, 1961.
32. Goh KC, Wang H, Yu N, et al: PLK1 as a potential drug target in cancer therapy. Drug Dev Res 62: 349-361, 2004.
33. Hayward DG, Newbatt Y, Pickard L, et al: Identification by high-throughput screening of viridin analogs as biochemical and cell-based inhibitors of the cell cycle-regulated nek2 kinase. J Biomol Screen 15: 918-927, 2010.
34. Burns S, Travers J, Collins I, et al: Identification of small-molecule inhibitors of protein kinase B (PKB/AKT) in an AlphaScreen high-throughput screen. J Biomol Screen 11: 822-827, 2006.