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Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
RESEARCH ARTICLE

Modified N,O-Nucleosides: Design, Synthesis, and Anti-tumour Activity

Loredana Maiuolo A D , Olga Bortolini B D , Antonio De Nino A , Beatrice Russo A , Riccardo Gavioli C and Fabio Sforza C
+ Author Affiliations
- Author Affiliations

A Dipartimento di Chimica e Tecnologie Chimiche, Università della Calabria, Via P. Bucci, 87036 Rende (CS), Italy.

B Dipartimento di Scienze Chimiche e Farmaceutiche, Università di Ferrara, Via Borsari 46, 44121 Ferrara, Italy.

C Dipartimento di Biochimica e Biologia Molecolare, Università di Ferrara, Via Fossato di Mortara 74, 44121 Ferrara, Italy.

D Corresponding authors. Email: maiuolo@unical.it; brl@unife.it

Australian Journal of Chemistry 67(4) 670-674 https://doi.org/10.1071/CH13511
Submitted: 25 September 2013  Accepted: 4 December 2013   Published: 23 January 2014

Abstract

A preliminary library of modified N,O-nucleosides was prepared and tested on a selected number of human cancer lines that include SKOV3, SW480, and K562. Thymine, N-benzyl substituents, and aromatic rings contribute to an increase of the biological activity, up to 10–25 μM, that appeared also reliant on the calculated lipophilicity of the nucleosides, expressed as cLogP, where P represents the partition coefficient of a solute between n-octanol and water.


References

[1]  B. D. Cheson, M. J. Keating, W. Plunkett, Nucleoside Analogs in Cancer Therapy 1997 (Marcel Dekker: New York).

[2]  E. De Clercq, Clin. Microbiol. Rev. 1997, 10, 674.
         | 1:STN:280:DyaK2svnslOgtw%3D%3D&md5=9e5c9e5d19b3048293b96103f4515cbaCAS | 9336668PubMed |

[3]  J. A. Secrist, Nucleic Acids Symp. Ser. 2005, 49, 15.
         | Crossref | GoogleScholarGoogle Scholar |

[4]  G. Romeo, U. Chiacchio, A. Corsaro, P. Merino, Chem. Rev. 2010, 110, 3337.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXjt1Gjs70%3D&md5=cd35ade82776a4328b5f6247180ab208CAS | 20232792PubMed |

[5]  A. Procopio, S. Alcaro, A. De Nino, L. Maiuolo, F. Ortuso, G. Sindona, Bioorg. Med. Chem. Lett. 2005, 15, 545.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXnsVKmtA%3D%3D&md5=f9c923917af20877e9d8da49ec8ba6bfCAS | 15664810PubMed |

[6]  O. Bortolini, A. De Nino, L. Maiuolo, B. Russo, G. Sindona, A. Tocci, Tetrahedron Lett. 2007, 48, 7125.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtVSksLzF&md5=2e14f505d3678a70f45613ff2aaef42dCAS |

[7]  U. Chiacchio, A. Padwa, G. Romeo, Curr. Org. Chem. 2009, 13, 422.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXkvVSnt74%3D&md5=85b4554e6e0ad2b1c9776768cc0f74feCAS |

[8]  R. Romeo, S. V. Giofrè, D. Iaria, M. T. Sciortino, S. Ronsisvalle, A. Chiacchio, A. Scala, Eur. J. Org. Chem. 2011, 5690.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtFersLnO&md5=7bb4eb89bb90ce0111a7f37671b32e36CAS |

[9]  J. R. Shelton, S. R. Burt, M. A. Peterson, Bioorg. Med. Chem. Lett. 2011, 21, 1484.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXit1Gmu7s%3D&md5=7a09db7847404ad6d9bb1c54801619e3CAS | 21288718PubMed |

[10]  M. A. Peterson, M. Oliveira, M. A. Christiansen, C. E. Cutler, Bioorg. Med. Chem. Lett. 2009, 19, 6775.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtlGisb%2FJ&md5=9227ec2035f7f30959931b79b303c4d9CAS | 19850476PubMed |

[11]  S. Miura, Y. Yoshimura, M. Endo, H. Machida, A. Matsuda, M. Tanaka, T. Sasaki, Cancer Lett. 1998, 129, 103.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXjvFOjt7c%3D&md5=61dfb44b560126cd223162d2c5eee761CAS | 9714341PubMed |

[12]  O. Bortolini, M. D’Agostino, A. De Nino, L. Maiuolo, M. Nardi, G. Sindona, Tetrahedron 2008, 64, 8078.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXoslegu78%3D&md5=0a4223ceae5777fea09a93fe8c97e58dCAS |

[13]  O. Bortolini, A. De Nino, T. Eliseo, R. Gavioli, L. Maiuolo, B. Russo, F. Sforza, Bioorg. Med. Chem. 2010, 18, 6970.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhtFyju7bL&md5=45b05a442e63e643df638e1feadea763CAS | 20813537PubMed |

[14]  R. H. Shoemaker, Nat. Rev. Cancer 2006, 6, 813.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XpvVCmu7c%3D&md5=b1d5f86b163fe598e8ec44f00251c2adCAS | 16990858PubMed |

[15]  S. Hatse, E. De Clercq, J. Balzarini, Biochem. Pharmacol. 1999, 58, 539.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXks1Wrs7g%3D&md5=e633a0d63a3df223ecae216e2f89aeb9CAS | 10413291PubMed |

[16]  O. Bortolini, I. Mulani, A. De Nino, L. Maiuolo, M. Nardi, B. Russo, S. Avnet, Tetrahedron 2011, 67, 5635.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXotVSjsrg%3D&md5=9a1b3e353e429d12f97f6a73a406f35fCAS |

[17]  C. A. Lipinski, F. Lombardo, B. W. Dominy, P. J. Feeney, Adv. Drug Deliv. Rev. 1997, 23, 3.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXktlKlsQ%3D%3D&md5=1854e3f92cffea022e6ee44f1659e845CAS |

[18]  F. Csizmadia, A. Tsantili-Kakoulidu, I. Panderi, F. Darvas, J. Pharm. Sci. 1997, 86, 865.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXjslCktLw%3D&md5=2e18635502f4ef755075a05e2b21e574CAS | 9232530PubMed |

[19]  J. Owens, Drug Discov. Today 2003, 8, 12.
         | Crossref | GoogleScholarGoogle Scholar |

[20]  M. Congreve, R. Carr, C. Murray, H. Jhoti, Drug Discov. Today 2003, 8, 876.
         | Crossref | GoogleScholarGoogle Scholar | 14554012PubMed |

[21]  C. R. Strauss, R. S. Varma, Top. Curr. Chem. 2006, 266, 199.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhsFersLg%3D&md5=5390a89c5ad73daa1b8e0731dcc45322CAS |

[22]  M. M. Andrade, M. T. Barros, R. C. Pintos, Tetrahedron 2008, 64, 10521.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXht1SntbjL&md5=f56a2cff46641ef702ffe68531bd4c68CAS |

[23]  T. Kano, T. Hashimoto, K. Maruoka, J. Am. Chem. Soc. 2005, 127, 11926.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXntVekurs%3D&md5=a4386332d24ae46e4776c80d1e69789aCAS | 16117516PubMed |

[24]  D. A. Evans, H.-J. Song, K. R. Fardrick, Org. Lett. 2006, 8, 3351.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XmtVSitLY%3D&md5=f55e02184a3dc475e2f678b34384bbc8CAS | 16836403PubMed |

[25]  P. Merino, S. Anoro, F. Merchan, T. Tejero, Heterocycles 2000, 53, 861.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXisVKrsL0%3D&md5=632c653c8a366f53d0e58dfbd9bc0516CAS |

[26]  P. Merino, S. Anoro, E. Cerrada, M. Laguna, A. Moreno, T. Tejero, Molecules 2001, 6, 208.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXjsFKitrk%3D&md5=6b83110526a9f5929d3f899912213716CAS |

[27]  R. Dalpozzo, A. De Nino, L. Maiuolo, A. Procopio, R. Romeo, G. Sindona, Synthesis 2002, 172.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xht1CntLg%3D&md5=b6fdd224cde5d01b4c4a71c3c872483bCAS |