Free Standard AU & NZ Shipping For All Book Orders Over $80!
Register      Login
Australian Journal of Chemistry Australian Journal of Chemistry Society
An international journal for chemical science
Shopping Cart: ( empty )
You are here: Home > Journals > CH > CH12059
RESEARCH FRONT
Contents Vol 65(9)

Transcription Inhibition by Organometallic Ruthenium–Arene Anticancer Complexes in Live Mammalian Cells

Astrid Astarina A , Mun Juinn Chow A and Wee Han Ang A B
+ Author Affiliations
- Author Affiliations

A Department of Chemistry, National University of Singapore, 3 Science Drive 3, 117543 Singapore.

B Corresponding author. Email: chmawh@nus.edu.sg

Australian Journal of Chemistry 65(9) 1271-1276 https://doi.org/10.1071/CH12059
Submitted: 31 January 2012  Accepted: 28 February 2012   Published: 28 May 2012

Abstract

Organometallic ruthenium–arene RAPTA complexes, currently being actively pursued as potential anticancer agents, interact with intracellular biological targets to form covalent adducts. Because their mode of action is still unclear, we investigated their binding with DNA and the ability of ruthenated-DNA adducts to elicit cellular responses such as transcription inhibition and repair. To investigate the influence of the spectator arene ligands on RAPTA activity, a novel RAPTA complex containing the bulky 1,3,5-triisopropylbenzene ligand was synthesized and characterized. Transcription experiments carried out in live mammalian cells using ruthenated plasmid probes revealed that increasing steric bulk of the arene ligand did not improve its ability to arrest transcription.


References

[1]  (a) L. Kelland, Nat. Rev. Cancer 2007, 7, 573.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXotVKru7c%3D&md5=25acd7c7d94dfa2eda1f478292ae5174CAS |
      (b) M. J. Clarke, F. Zhu, D. R. Frasca, Chem. Rev. 1999, 99, 2511.
         | Crossref | GoogleScholarGoogle Scholar |

[2]  (a) C. G. Hartinger, S. Zorbas-Seifried, M. A. Jakupec, B. Kynast, H. Zorbas, B. K. Keppler, J. Inorg. Biochem. 2006, 100, 891.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XksVCluro%3D&md5=cfbc278c2cfbb2bb223547cafdcb2cf9CAS |
      (b) A. Bergamo, G. Sava, Dalton Trans. 2007, 1267.
         | Crossref | GoogleScholarGoogle Scholar |
      (c) J. M. Rademaker-Lakhai, D. Van Den Bongard, D. Pluim, J. H. Beijnen, J. H. M. Schellens, Clin. Cancer Res. 2004, 10, 3717.
         | Crossref | GoogleScholarGoogle Scholar |
      (d) M. A. Jakupec, V. B. Arion, S. Kapitza, E. Reisner, A. Eichinger, M. Pongratz, B. Marian, N. Graf von Keyserlingk, B. K. Keppler, Int. J. Clin. Pharmacol. Ther. 2005, 43, 595.

[3]  E. Meggers, G. E. Atilla-Gokcumen, H. Bregman, J. Maksimoska, S. P. Mulcahy, N. Pagano, D. S. Williams, Synlett 2007, 2007, 1177.
         | Crossref | GoogleScholarGoogle Scholar |

[4]  W. F. Schmid, R. O. John, G. Muhlgassner, P. Heffeter, M. A. Jakupec, M. Galanski, W. Berger, V. B. Arion, B. K. Keppler, J. Med. Chem. 2007, 50, 6343.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXht12gs7%2FL&md5=d9f8c7950a25d218e13f1d7e8b18db0eCAS |

[5]  (a) R. E. Aird, J. Cummings, A. A. Ritchie, M. Muir, R. E. Morris, H. Chen, P. J. Sadler, D. I. Jodrell, Br. J. Cancer 2002, 86, 1652.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XkvVaitbg%3D&md5=3cc7dc57d3717692ceba553f2557b863CAS |
      (b) A. Bergamo, A. Masi, A. F. A. Peacock, A. Habtemariam, P. J. Sadler, G. Sava, J. Inorg. Biochem. 2010, 104, 79.
         | Crossref | GoogleScholarGoogle Scholar |

[6]  (a) W. H. Ang, P. J. Dyson, Eur. J. Inorg. Chem. 2006, 4003.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtFKjt7nF&md5=32718ad9c7e4d95a048dec3d65e92ab8CAS |
      (b) A. Levina, A. Mitra, P. A. Lay, Metallomics 2009, 1, 458.
         | Crossref | GoogleScholarGoogle Scholar |

[7]  (a) C. Scolaro, A. Bergamo, L. Brescacin, R. Delfino, M. Cocchietto, G. Laurenczy, T. J. Geldbach, G. Sava, P. J. Dyson, J. Med. Chem. 2005, 48, 4161.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXktlCrsL0%3D&md5=5f0e43578000584418f51b59633e5eccCAS |
      (b) A. Bergamo, A. Masi, P. J. Dyson, G. Sava, Int. J. Oncol. 2008, 33, 1281.

[8]  C. Scolaro, T. J. Geldbach, S. Rochat, A. Dorcier, C. Gossens, A. Bergamo, M. Cocchietto, I. Tavernelli, G. Sava, U. Rothlisberger, P. J. Dyson, Organometallics 2006, 25, 756.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xn&md5=4313677881b257e6d2b00f2f2883751bCAS |

[9]  Y. Jung, S. J. Lippard, Chem. Rev. 2007, 107, 1387.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXksFSgu7Y%3D&md5=034dd6ec08add4489ba11c5cd96cbb0eCAS |

[10]  R. C. Todd, S. J. Lippard, Metallomics 2009, 1, 280.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXlslWltb0%3D&md5=0058c243c87e35b23443abea4957b978CAS |

[11]  J. D. Page, I. Husain, A. Sancar, S. G. Chaney, Biochemistry 1990, 29, 1016.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3cXkvVemsw%3D%3D&md5=1f65f93fda99049ce3a8a1765674a1fdCAS |

[12]  (a) C. Scolaro, C. G. Hartinger, C. S. Allardyce, B. K. Keppler, P. J. Dyson, J. Inorg. Biochem. 2008, 102, 1743.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtVWit7rK&md5=77ea0def98c7be825534b9c7bcb7f045CAS |
      (b) W. H. Ang, E. Daldini, C. Scolaro, R. Scopelliti, L. Juillerat-Jeanneret, P. J. Dyson, Inorg. Chem. 2006, 45, 9006.
         | Crossref | GoogleScholarGoogle Scholar |

[13]  C. S. Allardyce, P. J. Dyson, D. J. Ellis, S. L. Heath, Chem. Commun. (Camb.) 2001, 1396.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXlt1ygtbc%3D&md5=2e4bf4a4f7b7d82db45b827cebd3c064CAS |

[14]  A. Ratanaphan, P. Temboot, P. J. Dyson, Chem. Biodivers. 2010, 7, 1290.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXmsF2jtLs%3D&md5=64355dc815aeeae7cdcef3cf437267a8CAS |

[15]  B. Wu, M. S. Ong, M. Groessl, Z. Adhireksan, C. G. Hartinger, P. J. Dyson, C. A. Davey, Chem. Eur. J. 2011, 17, 3562.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXjtFWnsLk%3D&md5=ff66dfbad9adc4b9b48ef15e7e8394caCAS |

[16]  P. Nowak-Sliwinska, J. R. van Beijnum, A. Casini, A. A. Nazarov, G. Wagnieres, H. van den Bergh, P. J. Dyson, A. W. Griffioen, J. Med. Chem. 2011, 54, 3895.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXmtFWqs7s%3D&md5=cd26da74665b185c21fb86b8ea15b68bCAS |

[17]  W. H. Ang, M. Myint, S. J. Lippard, J. Am. Chem. Soc. 2010, 132, 7429.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXls1yqu7o%3D&md5=c3f73991dac211f5b9091422df7fb1c2CAS |

[18]  (a) H. Horvath, G. Laurenczy, A. Katho, J. Organomet. Chem. 2004, 689, 1036.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhslWitrk%3D&md5=79c2035745917300825f8c077def23aeCAS |
      (b) A. Casini, C. Gabbiani, F. Sorrentino, M. P. Rigobello, A. Bindoli, T. J. Geldbach, A. Marrone, N. Re, C. G. Hartinger, P. J. Dyson, L. Messori, J. Med. Chem. 2008, 51, 6773.
         | Crossref | GoogleScholarGoogle Scholar |
      (c) W. H. Ang, E. Daldini, L. Juillerat-Jeanneret, P. J. Dyson, Inorg. Chem. 2007, 46, 9048.
         | Crossref | GoogleScholarGoogle Scholar |
      (d) A. K. Renfrew, A. D. Phillips, E. Tapavicza, R. Scopelliti, U. Rothlisberger, P. J. Dyson, Organometallics 2009, 28, 5061.
         | Crossref | GoogleScholarGoogle Scholar |
      (e) W. H. Ang, L. J. Parker, A. De Luca, L. Juillerat-Jeanneret, C. J. Morton, M. Lo Bello, M. W. Parker, P. J. Dyson, Angew. Chem. Int. Ed. 2009, 48, 3854.
         | Crossref | GoogleScholarGoogle Scholar |

[19]  W. L. de Laat, N. G. J. Jaspers, J. H. J. Hoeijmakers, Genes Dev. 1999, 13, 768.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXisF2isrw%3D&md5=615b1fdb6b2047df0b972e2e4606f9a4CAS |

[20]  F. Gao, X. Chen, J.-Q. Wang, Y. Chen, H. Chao, L.-N. Ji, Inorg. Chem. 2009, 48, 5599.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXmvFWqsr8%3D&md5=a6e88e5528f44cc70f286a10109f652eCAS |

[21]  SMART ver. 5.628 (Bruker AXS Inc.) 2001 (Madison, WI).

[22]  SAINT+ ver. 6.22a (Bruker AXS Inc.) 2001 (Madison, WI).

[23]  SADABS ver. 2.10 (G. W. Sheldrick) 2001 (University of Gottingen, Gottingen, Germany).

[24]  SHELXTL ver. 6.14 (Bruker AXS Inc.) 2000 (Madison, WI).