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Synthesis and in vitro biological evaluation of novel 2-aminoimidazolone derivatives as anti-tumor agents

You-An Xiao ,  Zhi-Qiang Wang ,  Xue-Min Wang ,  Yi Hui ,  Yong Ling ,  Xin-Yang Wang ,  Li-Qin He

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Citation:  You-An Xiao, Zhi-Qiang Wang, Xue-Min Wang, Yi Hui, Yong Ling, Xin-Yang Wang, Li-Qin He. Synthesis and in vitro biological evaluation of novel 2-aminoimidazolone derivatives as anti-tumor agents[J]. Chinese Chemical Letters, 2013, 24(8): 727-730. shu

Synthesis and in vitro biological evaluation of novel 2-aminoimidazolone derivatives as anti-tumor agents

    • 通讯作者: Yong Ling,
    Li-Qin He,
摘要: Novel 2-aminoimidazolone derivatives were synthesized. Most compounds displayed strong anticancer activities against human carcinoma cells in vitro. Compounds 8a, 8b and 8j exhibited optimal activity superior to 5-FU in most cancer cells tested. Especially, the IC50s of 8b (12.6-21.5 μmol/L) against five tumor cells were 1-4 fold less than those of 5-FU (18.4-56.1 μmol/L) in vitro. Furthermore, compound 8b could induce SMMC-7721 cell apoptosis in a dose-dependent manner. Therefore, our novel findingsmay provide a new framework for the design of new 2-aminoimidazolone derivatives for the treatment of cancer.

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    1. [1] P. Boyle, B. Levin (Eds.), World Cancer Report, WHO International Agency for Research on Cancer, Lyon, France, 2008.[1] P. Boyle, B. Levin (Eds.), World Cancer Report, WHO International Agency for Research on Cancer, Lyon, France, 2008.

    2. [2] R. Breinbauer, M. Manger, M. Scheck, et al., Natural product guided compound library development, Curr. Med. Chem. 9 (2002) 2129-2145.[2] R. Breinbauer, M. Manger, M. Scheck, et al., Natural product guided compound library development, Curr. Med. Chem. 9 (2002) 2129-2145.

    3. [3] Y.W. Guo, E. Trivellone, Ent-untenospongin A, a new C21 furanoterpene from the Indian marine sponge Hippospongia sp., Chin. Chem. Lett. 11 (2000) 327-330.[3] Y.W. Guo, E. Trivellone, Ent-untenospongin A, a new C21 furanoterpene from the Indian marine sponge Hippospongia sp., Chin. Chem. Lett. 11 (2000) 327-330.

    4. [4] A. Aiello, E. Fattorusso, C. Imperatore, et al., Zorrimidazolone, a bioactive alkaloid from the non-indigenous Mediterranean Stolidobranch Polyandrocarpa zorritensis, Mar. Drugs 9 (2011) 1157-1165.[4] A. Aiello, E. Fattorusso, C. Imperatore, et al., Zorrimidazolone, a bioactive alkaloid from the non-indigenous Mediterranean Stolidobranch Polyandrocarpa zorritensis, Mar. Drugs 9 (2011) 1157-1165.

    5. [5] A.D. Rohan, W. Aalbersberg, S. Meo, et al., The isolation and synthesis of polyandrocarpamines A and B. Two new 2-aminoimidazolone compounds from the Fijian ascidian Polyandrocarpa sp., Tetahedron 58 (2002) 3263.[5] A.D. Rohan, W. Aalbersberg, S. Meo, et al., The isolation and synthesis of polyandrocarpamines A and B. Two new 2-aminoimidazolone compounds from the Fijian ascidian Polyandrocarpa sp., Tetahedron 58 (2002) 3263.

    6. [6] A.D. Rohan, S.B. Paul, E.N. Juliette, et al., A microwave-assisted stereoselective synthesis of polyandrocarpamines A and B, Tetrahedron Lett. 50 (2009) 880-882.[6] A.D. Rohan, S.B. Paul, E.N. Juliette, et al., A microwave-assisted stereoselective synthesis of polyandrocarpamines A and B, Tetrahedron Lett. 50 (2009) 880-882.

    7. [7] M.F. Pilar, M. Pedro, A.S. Miguel, A convergent approach to midpacamide and dispacamide pyrrole-imidazole marine alkaloids, Tetrahedron Lett. 42 (2001) 851-854.[7] M.F. Pilar, M. Pedro, A.S. Miguel, A convergent approach to midpacamide and dispacamide pyrrole-imidazole marine alkaloids, Tetrahedron Lett. 42 (2001) 851-854.

    8. [8] J.C. Boehm, J.G. Gleason, I. Pendrak, et al., Synthesis and LTB4 receptor antagonist activities of the naturally occurring LTB4 receptor antagonist Leucettamine A and related analogues, J. Med. Chem. 36 (1993) 3333-3340.[8] J.C. Boehm, J.G. Gleason, I. Pendrak, et al., Synthesis and LTB4 receptor antagonist activities of the naturally occurring LTB4 receptor antagonist Leucettamine A and related analogues, J. Med. Chem. 36 (1993) 3333-3340.

    9. [9] A.D. Rohan, H. Andreas, O. Asiah, et al., A class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing, J. Med. Chem. 54 (2011) 4172-4186.[9] A.D. Rohan, H. Andreas, O. Asiah, et al., A class of potent inhibitors of cdc2-like kinases and dual specificity, tyrosine phosphorylation regulated kinases derived from the marine sponge leucettamine B: modulation of alternative pre-RNA splicing, J. Med. Chem. 54 (2011) 4172-4186.

    10. [10] M. Debdab, S. Renault, O. Lozach, et al., Synthesis and preliminary biological evaluation of new derivatives of the marine alkaloid leucettamine B as kinase inhibitors, Eur. J. Med. Chem. 45 (2010) 805-810.[10] M. Debdab, S. Renault, O. Lozach, et al., Synthesis and preliminary biological evaluation of new derivatives of the marine alkaloid leucettamine B as kinase inhibitors, Eur. J. Med. Chem. 45 (2010) 805-810.

    11. [11] B.K. Park, N.R. Kitteringham, P.M. O'Neill, Metabolism of fluorine-containing drugs, Annu. Rev. Pharmacool. Toxicol. 41 (2001) 443-470.[11] B.K. Park, N.R. Kitteringham, P.M. O'Neill, Metabolism of fluorine-containing drugs, Annu. Rev. Pharmacool. Toxicol. 41 (2001) 443-470.

    12. [12] K.L. Kirk, R. Filler, Recent advances in the biomedicinal chemistry of fluorinecontaining compounds, in: I. Ojima, J.R. McCarthy, T. Welch (Eds.), Biomedical Frontiers of Fluorine Chemistry, ACS Symposium Series No. 639, American Chemical Society, Washington, DC, 1996, pp. 1-24.[12] K.L. Kirk, R. Filler, Recent advances in the biomedicinal chemistry of fluorinecontaining compounds, in: I. Ojima, J.R. McCarthy, T. Welch (Eds.), Biomedical Frontiers of Fluorine Chemistry, ACS Symposium Series No. 639, American Chemical Society, Washington, DC, 1996, pp. 1-24.

    13. [13] N. Mulakayala, B. Kandagatla, Ismail, et al., InCl3-catalysed synthesis of 2-aryl quinazolin-4(3H)-ones and 5-aryl pyrazolo [4,3-d] pyrimidin-7(6H)-ones and their evaluation as potential anticancer agents, Bioorg. Med. Chem. Lett. 22 (2012) 5063-5066.[13] N. Mulakayala, B. Kandagatla, Ismail, et al., InCl3-catalysed synthesis of 2-aryl quinazolin-4(3H)-ones and 5-aryl pyrazolo [4,3-d] pyrimidin-7(6H)-ones and their evaluation as potential anticancer agents, Bioorg. Med. Chem. Lett. 22 (2012) 5063-5066.

    14. [14] Y. Liu, W. Zhong, S. Li, Syntheses and studies of hydantoin derivatives as potential anti-tuberculosis inhibitors, Chin. Chem. Lett. 23 (2012) 133-136.[14] Y. Liu, W. Zhong, S. Li, Syntheses and studies of hydantoin derivatives as potential anti-tuberculosis inhibitors, Chin. Chem. Lett. 23 (2012) 133-136.

    15. [15] The data of selected compounds: 8a: Yield 75%, mp > 250℃. MS (ESI): m/z 270[M+1]+. 1H NMR (300 MHz, CDCl3): δ 7.60 (s, 1H), 7.33 (s, 1H), 7.11 (s, 1H), 7.02 (m, 1H), 6.74 (m, 1H). Anal. calcd. for C11H9F2N3O3: C 49.02, H 3.38, N 15.56; Found: C 49.08, H 3.37, N 15.61. 8b: Yield 71%,mp > 250℃. MS (ESI): m/z 284[M+1]+. 1 3): δ 7.80 (s, 1H), 7.43 (s, 1H), 7.26 (S, 1H), 7.01 (m, 1H), 6.82 (m, 1H), 2.48-2.47 (d, 3H, J = 9.0 Hz). Anal. calcd. forC12H11F2N3O3: C 50.82, H 3.98, N 14.82; Found: C 50.89, H 3.91, N 14.84. 8j: Yield 70%, mp > 250℃. MS (ESI): m/z 358 [M+1]+. 1H NMR (300MHz, CDCl3): 7.41-7.30 (s, 1H, C=CH), 7.21 (s, 1H, CF2H), 7.09-7.04 (m, 2H, Ar-H), 6.46 (d, 1H, Ar-H), 3.72-3.60 (m, 3H, HOCH2, HOCH), 3.07(d, 3H, CH3), 2.80-2.72 (m, 2H, NHCH2). Anal. calcd. for C15H17F2N3O5: C 50.35, H 4.88, N 11.68; Found: C 50.42, H 4.80, N 11.76.[15] The data of selected compounds: 8a: Yield 75%, mp > 250℃. MS (ESI): m/z 270[M+1]+. 1H NMR (300 MHz, CDCl3): δ 7.60 (s, 1H), 7.33 (s, 1H), 7.11 (s, 1H), 7.02 (m, 1H), 6.74 (m, 1H). Anal. calcd. for C11H9F2N3O3: C 49.02, H 3.38, N 15.56; Found: C 49.08, H 3.37, N 15.61. 8b: Yield 71%,mp > 250℃. MS (ESI): m/z 284[M+1]+. 1 3): δ 7.80 (s, 1H), 7.43 (s, 1H), 7.26 (S, 1H), 7.01 (m, 1H), 6.82 (m, 1H), 2.48-2.47 (d, 3H, J = 9.0 Hz). Anal. calcd. forC12H11F2N3O3: C 50.82, H 3.98, N 14.82; Found: C 50.89, H 3.91, N 14.84. 8j: Yield 70%, mp > 250℃. MS (ESI): m/z 358 [M+1]+. 1H NMR (300MHz, CDCl3): 7.41-7.30 (s, 1H, C=CH), 7.21 (s, 1H, CF2H), 7.09-7.04 (m, 2H, Ar-H), 6.46 (d, 1H, Ar-H), 3.72-3.60 (m, 3H, HOCH2, HOCH), 3.07(d, 3H, CH3), 2.80-2.72 (m, 2H, NHCH2). Anal. calcd. for C15H17F2N3O5: C 50.35, H 4.88, N 11.68; Found: C 50.42, H 4.80, N 11.76.

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  • 收稿日期:  2013-03-13
  • 网络出版日期:  2013-04-26
通讯作者: 陈斌, bchen63@163.com
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