Synthesis and biological evaluation of 1,9-disubstituted β-carbolines as potent DNA intercalating and cytotoxic agents

European Journal of Medicinal Chemistry

Volumn 46, Issue 10, 2011, Pages 5127-5137

  Chen, Zhiyong ^a   Cao, Rihui ^b   Shi, Buxi ^b   Guo, Liang ^c   Sun, Jie ^c   Ma, Qin ^c   Fan, Wenxi ^c   Song, Huacan ^b  

^a Guangzhou) Guangzhou   (China)

^b SUN YAT SEN UNIVERSITY   (China)

^c Xinjiang Huashidan Pharmaceutical Co Ltd   (China)

Author keywords

Carboline; Cytotoxic; Intercalating; Synthesis; T m

Indexed keywords

1 [N (2 DIETHYLAMINO)ETHYL]METHYLAMINO 9 (3 CHLOROBENZYL) BETA CARBOLINE SALT; 1 [N (2 DIETHYLAMINO)ETHYL]METHYLAMINO 9 (3 PHENYLPROPYL) BETA CARBOLINE SALT; 1 [N (2 DIETHYLAMINO)ETHYL]METHYLAMINO 9 (4 FLUOROBENZYL) BETA CARBOLINE SALT; 1 [N (2 DIETHYLAMINO)ETHYL]METHYLAMINO 9 BENZYL BETA CARBOLINE SALT; 1 [N (2 DIETHYLAMINO)ETHYL]METHYLAMINO 9 ISOBUTYL BETA CARBOLINE SALT; 1 [N (2 DIETHYLAMINO)ETHYL]METHYLAMINO 9 N BUTYL BETA CARBOLINE SALT; 1 [N (3 DIETHYLAMINO)PROPYL]METHYLAMIN 9 (4 FLUOROBENZYL) BETA CARBOLINE SALT; 1 [N (3 DIETHYLAMINO)PROPYL]METHYLAMINO 9 (3 CHLOROBENZYL) BETA CARBOLINE SALT; 1 [N (3 DIETHYLAMINO)PROPYL]METHYLAMINO 9 (3 PHENYLPROPYL) BETA CARBOLINE SALT; 1 [N (3 DIETHYLAMINO)PROPYL]METHYLAMINO 9 BENZYL BETA; 1 [N (3 DIETHYLAMINO)PROPYL]METHYLAMINO 9 ISOBUTYL BETA CARBOLINE SALT; 1 [N (3 DIETHYLAMINO)PROPYL]METHYLAMINO 9 N BUTYL BETA CARBOLINE SALT; 1 [N (3 DIMETHYLAMINO)PROPYL]METHYLAMINO 9 (3 CHLOROBENZYL) BETA CARBOLINE SALT; 1 [N (3 DIMETHYLAMINO)PROPYL]METHYLAMINO 9 (3 PHENYLPROPYL) BETA CARBOLINE SALT; 1 [N (3 DIMETHYLAMINO)PROPYL]METHYLAMINO 9 (4 FLUOROBENZYL) BETA CARBOLINE SALT; 1 [N (3 DIMETHYLAMINO)PROPYL]METHYLAMINO 9 ISOBUTYL BETA CARBOLINE SALT; 1 [N (3 DIMETHYLAMINO)PROPYL]METHYLAMINO 9 N BUTYL BETA CARBOLINE SALT; 1 [N (4 DIETHYLAMINO)BUTYL]METHYLAMINO 9 (3 CHLOROBENZYL) BETA CARBOLINE SALT; 1 [N (4 DIETHYLAMINO)BUTYL]METHYLAMINO 9 (3 PHENYLPROPYL) BETA CARBOLINE SALT; 1 [N (4 DIETHYLAMINO)BUTYL]METHYLAMINO 9 (4 FLUOROBENZYL) BETA CARBOLINE SALT; 1 [N (4 DIETHYLAMINO)BUTYL]METHYLAMINO 9 BENZYL BETA CARBOLINE SALT; 1 [N (4 DIETHYLAMINO)BUTYL]METHYLAMINO 9 ISOBUTYL BETA CARBOLINE SALT; 1 [N (4 DIETHYLAMINO)BUTYL]METHYLAMINO 9 N BUTYL BETA CARBOLINE SALT; AMINO ACID DERIVATIVE; ANTINEOPLASTIC AGENT; BENZYL DERIVATIVE; CARBOLINE DERIVATIVE; CYTOTOXIC AGENT; DNA; INTERCALATING AGENT; UNCLASSIFIED DRUG;

ARTICLE; CANCER CELL CULTURE; CYTOTOXICITY; DRUG POTENCY; DRUG SYNTHESIS; FLUORESCENCE SPECTROSCOPY; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; IC 50; IN VITRO STUDY; PHARMACOPHORE;

ANTINEOPLASTIC AGENTS; CARBOLINES; CELL LINE, TUMOR; CYTOTOXINS; DNA; DRUG SCREENING ASSAYS, ANTITUMOR; HUMANS; INHIBITORY CONCENTRATION 50; INTERCALATING AGENTS; NEOPLASMS;

EID: 80053185089     PISSN: 02235234     EISSN: 17683254     Source Type: Journal    
DOI: 10.1016/j.ejmech.2011.08.027     Document Type: Article

References (32)

1. M.F. Braña, M. Cacho, A. Gradillas, B. Pascual-Teresa, and A. Ramos Intercalators as anticancer drugs Curr. Pharm. Des 7 2001 1745 1780 (Pubitemid 32998336)
2. M. Demeunynck, C. Bailly, and W.D. Wilson DNA and RNA binders 2003 Wiley-VCH Weinheim
3. R. Cao, W. Peng, Z. Wang, and A. Xu β-Carboline alkaloids: biochemical & pharmacological functions Curr. Med. Chem. 14 2007 479 500
4. J. Ishida, H.K. Wang, K.F. Bastow, C.Q. Hu, and K.H. Lee Antitumor agents 201. Cytotoxicity of harmine and β-carboline analogs Bioorg. Med. Chem. Lett. 9 1999 3319 3324
5. S. Xiao, W. Lin, C. Wang, and M. Yang Synthesis and biological evaluation of DNA targeting flexible side-chain substituted β-carboline derivatives Bioorg. Med. Chem. Lett. 11 2001 437 441 (Pubitemid 32165203)
6. Y.C. Shen, C.Y. Chen, P.W. Hsieh, C.Y. Duh, Y.M. Lin, and C.L. Ko The preparation and evaluation of 1-substituted 1,2,3,4-tetrahydro- and 3,4-dihydro-β-carboline derivatives as potential antitumor agents Chem. Pharm. Bull. 53 2005 32 36
7. A.M. Deveau, M.A. Labroli, C.M. Dieckhaus, M.T. Barthen, K.S. Smith, and T.L. Macdonald The synthesis of amino-acid functionalized β-carbolines as topoisomerase II inhibitors Bioorg. Med. Chem. Lett. 11 2001 1251 1255 (Pubitemid 32434345)
8. M. Zhao, L. Bi, W. Wang, C. Wang, M. Baudy-Floc'h, J. Ju, and S. Peng Synthesis and cytotoxic activities of β-carboline amino acid ester conjugates Bioorg. Med. Chem. 14 2006 6998 7010 (Pubitemid 44307639)
9. A.S.N. Formagio, L.T.D. Dusman, M.A. Foglio, C. Madjarof, J.E. Carvalho, W.F. Costa, F.P. Cardoso, and M.H. Sarragiotto Synthesis and antitumoral activity of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) β-carboline derivatives Bioorg. Med. Chem. 16 2008 9660 9667
10. J. Wu, M. Zhao, K. Qian, K.-H. Lee, S. Morris-Natschke, and S. Peng Novel N-(3-carboxyl-9-benzyl-β-carboline-1-yl)ethylamino acids: synthesis, anti-tumor evaluation, intercalating determination, 3D QSAR analysis and docking investigation Eur. J. Med. Chem. 44 2009 4153 4161
11. Y. Boursereau, and I. Coldham Synthesis and biological studies of 1-amino β-carbolines Bioorg. Med. Chem. Lett. 14 2004 5841 5844 (Pubitemid 39421528)
12. W. Jiang, C. Charlet-Fagnere, J. Sapi, J.-Y. Laronze, P. Renard, B. Pfeiffer, and S. Leonce Cytotoxic bis-3,4-dihydro-β-carbolines and bis-β-carbolines J. Enzyme Inhib. Med. Chem. 17 2002 369 374
13. K. Hayashi, M. Nagao, and T. Sugimura Interactions of norharman and harman with DNA Nucleic Acids Res. 4 1977 3679 3685 (Pubitemid 8216259)
14. Y. Funayama, K. Nishio, K. Wakabayashi, M. Nagao, K. Shimoi, T. Ohira, S. Hasegawa, and M. Saijo Effects of beta- and gamma-carboline derivates of DNA topoisomerase activities Mutat. Res. 349 1996 183 191
15. A.M. Sobhani, S.A. Ebrahimi, and M. Mahmoudian An in vitro evaluation of human DNA topoisomerase I inhibition by Peganum harmala L. seeds extract and its beta-carboline alkaloids J. Pharm. Pharm. Sci. 5 2002 19 23 (Pubitemid 34463347)
16. Y. Song, J. Wang, S.F. Teng, D. Kesuma, Y. Deng, J. Duan, J.H. Wang, R.Z. Qi, and M.M. Sim β-Carbolines as specific inhibitors of cyclin-Dependent kinases Bioorg. Med. Chem. Lett. 12 2002 1129 1132 (Pubitemid 34242818)
17. Y. Song, D. Kesuma, J. Wang, Y. Deng, J. Duan, J.H. Wang, and R.Z. Qi Specific inhibition of cyclin-dependent kinases and cell proliferation by harmine Biochem. Biophys. Res. Commun. 317 2004 128 132 (Pubitemid 38401973)
18. Y. Li, F. Liang, W. Jiang, F. Yu, R. Cao, Q. Ma, X. Dai, J. Jiang, Y. Wang, and S. Si DH334, a β-carboline anti-cancer drug, inhibits the CDK activity of budding yeast Cancer Biol. Ther. 6 2007 1193 1199 (Pubitemid 351590371)
19. A.C. Castro, L.C. Dang, F. Soucy, L. Grenier, H. Mazdiyasni, M. Hottelet, L. Parent, C. Pien, V. Palombella, and J. Adams Novel IKK inhibitors: β-carbolines Bioorg. Med. Chem. Lett. 13 2003 2419 2422
20. J.I. Trujillo, M.J. Meyers, D.R. Anderson, S. Hegde, M.W. Mahoney, W.F. Vernier, I.P. Buchler, K.K. Wu, S. Yang, S.J. Hartmann, and D.B. Reitz Novel tetrahydro-β-carboline-1-carboxylic acids as inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2) Bioorg. Med. Chem. Lett. 17 2007 4657 4663 (Pubitemid 47061507)
21. J. Zhang, Y. Li, L. Guo, R. Cao, P. Zhao, W. Jiang, Q. Ma, H. Yi, Z. Li, J. Jiang, J. Wu, Y. Wang, and S. Si DH166, a beta-carboline derivative, inhibits the kinase activity of PLK1 Cancer Biol. Ther. 8 2009 2374 2383
22. P.A. Barsanti, W. Wang, Z. Ni, D. Duhl, N. Brammeier, and E. Martin The discovery of tetrahydro-β-carbolines as inhibitors of the kinesin Eg5 Bioorg. Med. Chem. Lett. 20 2010 157 160
23. R. Cao, W. Peng, H. Chen, Y. Ma, X. Liu, X. Hou, H. Guan, and A. Xu DNA binding properties of 9-substituted harmine derivatives Biochem. Biophys. Res. Co 338 2005 1557 1563 (Pubitemid 41608427)
24. R. Cao, Q. Chen, X. Hou, H. Chen, H. Guan, Y. Ma, W. Peng, and A. Xu Synthesis, acute toxicities, and antitumor effects of novel 9-substituted β-carboline derivatives Bioorg. Med. Chem. 12 2004 4613 4623 (Pubitemid 39055982)
25. R. Cao, W. Peng, H. Chen, X. Hou, H. Guan, Q. Chen, Y. Ma, and A. Xu Synthesis and in vitro cytotoxic evaluation of 1,3-bisubstituted and 1,3,9-trisubstituted β-carboline derivatives Eur. J. Med. Chem. 40 2005 249 257 (Pubitemid 40255767)
26. R. Cao, H. Chen, W. Peng, Y. Ma, X. Hou, H. Guan, X. Liu, and A. Xu Design, synthesis and in vitro and in vivo antitumor activities of novel β-carboline derivatives Eur. J. Med. Chem. 40 2005 991 1001 (Pubitemid 41421104)
27. H. Guan, H. Chen, W. Peng, Y. Ma, R. Cao, X. Liu, and A. Xu Design of β-carboline derivatives as DNA-targeting antitumor agents Eur. J. Med. Chem. 41 2006 1167 1179 (Pubitemid 44566416)
28. R. Cao, W. Yi, Q. Wu, X. Guan, M. Feng, C. Ma, Z. Chen, H. Song, and W. Peng Synthesis and cytotoxic activities of 1-benzylidine substituted β-carboline derivatives Bioorg. Med. Chem. Lett. 18 2008 6558 6561
29. Q. Wu, R. Cao, M. Feng, X. Guan, C. Ma, J. Liu, H. Song, and W. Peng Synthesis and in vitro cytotoxic evaluation of novel 3,4,5-trimethoxyphenyl substituted β-carboline derivatives Eur. J. Med. Chem. 44 2009 533 540
30. H.R. Snyder, S.M. Parmerter, and L. Katz The synthesis of derivatives of β-carboline. III. The nitration of harman J. Am. Chem. Soc. 70 1948 222 225
31. Z. Chen, R. Cao, B. Shi, W. Yi, L. Yu, H. Song, Z. Ren, and W. Peng Synthesis of novel β-carbolines with efficient DNA-binding capacity and potent cytotoxicity Bioorg. Med. Chem. Lett. 20 2010 3876 3879
32. Z. Chen, R. Cao, L. Yu, B. Shi, J. Sun, L. Guo, Q. Ma, W. Yi, X. Song, and H. Song Synthesis, cytotoxic activities and DNA binding properties of β-carboline derivatives Eur. J. Med. Chem. 45 2010 4740 4745