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 > CH21049
RESEARCH ARTICLE
Contents Vol 74(7)

The Synthesis and Biological Evaluation of Some C-9 and C-10 Substituted Derivatives of the RNA Polymerase I Transcription Inhibitor CX-5461

Madushani Amarasiri A , Yen Vo A , Michael G. Gardiner A , Perlita Poh B , Priscilla Soo B , Megan Pavy B , Nadine Hein B , Rita Ferreira B , Katherine M. Hannan B , Ross D. Hannan B C D E F H and Martin G. Banwell https://orcid.org/0000-0002-0582-475X A G H
+ Author Affiliations
- Author Affiliations

A Research School of Chemistry, Institute of Advanced Studies, The Australian National University, Canberra, ACT 2601, Australia.

B ACRF Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia.

C Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Vic. 3010, Australia.

D Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, Vic. 3000, Australia.

E Department of Biochemistry and Molecular Biology, Monash University, Clayton, Vic. 3800, Australia.

F School of Biomedical Sciences, University of Queensland, Brisbane, Qld 4072, Australia.

G Institute for Advanced and Applied Chemical Synthesis, Jinan University, Guangzhou 510632, China.

H Corresponding authors. Email: Ross.Hannan@anu.edu.au; Martin.Banwell@anu.edu.au

Australian Journal of Chemistry 74(7) 540-556 https://doi.org/10.1071/CH21049
Submitted: 16 February 2021  Accepted: 16 March 2021   Published: 16 April 2021

Abstract

The regio-isomeric alkynyl-substituted derivatives, 2 and 3, of the RNA Polymerase I (Pol I) transcription inhibitor CX-5461 (1) were prepared and the active one (compound 3) subjected to click reactions ([3 + 2]-cycloaddition reactions) with certain alkyl azides bearing biotin or fluorescent tags. Compounds 2 and 3, as well as four [3 + 2]-cycloadducts of the latter, were subjected to biological evaluation in a human acute myeloid leukemia cell line model. Among the six compounds tested only alkyne 3 remained active but this was less potent than parent 1.

Keywords: alkyne, azide, biotin, cancer, click chemistry, fluorescent, ribosomal RNA, RNA Polymerase 1 inhibitor, synthesis, tagging.


References

[1]  (a) D. Ruggero, P. P. Pandolfi, Nat. Rev. Cancer 2003, 3, 179.
         | Crossref | GoogleScholarGoogle Scholar | 12612653PubMed |
      (b) W. J. Andrews, T. Panova, C. Normand, O. Gadal, I. G. Tikhonova, K. I. Panov, J. Biol. Chem. 2013, 288, 4567.
         | Crossref | GoogleScholarGoogle Scholar |

[2]  (a) R. J. White, Nat. Rev. Mol. Cell Biol. 2005, 6, 69.
         | Crossref | GoogleScholarGoogle Scholar | 15688068PubMed |
      (b) D. Williamson, Y. J. Lu, C. Fang, K. Pritchard-Jones, J. Shipley, Genes Chromosomes Cancer 2006, 45, 839.
         | Crossref | GoogleScholarGoogle Scholar |
      (c) D. Drygin, W. G. Rice, I. Grummt, Annu. Rev. Pharmacol. 2010, 50, 131.
         | Crossref | GoogleScholarGoogle Scholar |
      (d) D. Drygin, A. Lin, J. Bliesath, C. B. Ho, S. E. O’Brien, C. Proffitt, M. Omori, M. Haddach, M. K. Schwaebe, A. Siddiqui-Jain, N. Streiner, J. E. Quin, E. Sanij, M. J. Bywater, R. D. Hannan, D. Ryckman, K. Anderes, W. G. Rice, Cancer Res. 2011, 71, 1418.
         | Crossref | GoogleScholarGoogle Scholar |
      (e) K. M. Hannan, E. Sanij, L. I. Rothblum, R. D. Hannan, R. B. Pearson, Biochim. Biophys. Acta 2013, 1829, 342.
         | Crossref | GoogleScholarGoogle Scholar |

[3]  (a) B. Vogelstein, K. W. Kinzler, Nat. Med. 2004, 10, 789.
         | Crossref | GoogleScholarGoogle Scholar | 15286780PubMed |
      (b) N. Hein, K. M. Hannan, A. J. George, E. Sanij, R. D. Hannan, Trends Mol. Med. 2013, 19, 643.
         | Crossref | GoogleScholarGoogle Scholar |
      (c) C. Villicaña, G. Cruz, M. Zurita, Cancer Cell Int. 2014, 14, 18.
         | Crossref | GoogleScholarGoogle Scholar |

[4]  (a) M. Haddach, M. K. Schwaebe, J. Michaux, J. Nagasawa, S. E. O’Brien, J. P. Whitten, F. Pierce, P. Kerdoncuff, L. Darjania, R. Stansfield, D. Drygin, K. Anderes, C. Proffitt, J. Bliesath, A. Siddiqui-Jain, M. Omori, N. Huser, W. G. Rice, D. M. Ryckman, ACS Med. Chem. Lett. 2012, 3, 602.
         | Crossref | GoogleScholarGoogle Scholar | 24900516PubMed |
      (b) M. J. Bywater, G. Poortinga, E. Sanij, N. Hein, A. Peck, C. Cullinane, M. Wall, L. Cluse, D. Drygin, K. Anderes, N. Huser, C. Proffitt, J. Bliesath, M. Haddaach, M. K. Schwaebe, D. M. Ryckamn, W. G. Rice, C. Schmitt, S. W. Lowe, R. W. Johnstone, R. B. Pearson, G. A. McArthur, R. D. Hannan, Cancer Cell 2012, 22, 51.
         | Crossref | GoogleScholarGoogle Scholar |

[5]  (a) A. W. Y. Leung, M. Anantha, W. H. Dragowska, M. Wehbe, M. B. Bally, J. Control. Release 2018, 286, 1.and references cited therein.
         | Crossref | GoogleScholarGoogle Scholar |
      (b) A. Khot, N. Brajanovski, D. P. Cameron, N. Hein, K. H. Maclachlan, E. Sanij, J. Lim, J. Soong, E. Link, P. Blombery, E. R. Thompson, A. Fellowes, K. E. Sheppard, G. A. McArthur, R. B. Pearson, R. D. Hannan, G. Poortinga, S. J. Harrison, Cancer Discov. 2019, 9, 1036.
         | Crossref | GoogleScholarGoogle Scholar |
      (c) H.-J. Sullivan, B. Chen, C. Wu, J. Chem. Inf. Model. 2020, 60, 5203.and references cited therein
         | Crossref | GoogleScholarGoogle Scholar |

[6]  R. Ferreira, J. S. Schneekloth, K. I. Panov, K. M. Hannan, R. D. Hannan, Cells 2020, 9, 266.
         | Crossref | GoogleScholarGoogle Scholar |

[7]  L. E. Kerry, E. E. Pegg, D. P. Cameron, J. Budzak, G. Poortinga, K. M. Hannan, R. D. Hannan, G. Rudenko, PLoS Negl. Trop. Dis. 2017, 11, e0005432.
         | Crossref | GoogleScholarGoogle Scholar | 28263991PubMed |

[8]  O. N. Kostopoulou, V. Wilhelmi, S Raiss, S Ananthaseshan, M. S. Lindström, J Bartek, C Söderberg-Naucler, Oncotarget 2017, 8, 96536.
         | Crossref | GoogleScholarGoogle Scholar | 29228551PubMed |

[9]  (a) For discussion of such matters see, for example: J. E. Quin, J. R. Devlin, D. Cameron, K. M. Hannan, R. B. Pearson, R. D. Hannan, Biochim. Biophys. Acta 2014, 1842, 802.
         | Crossref | GoogleScholarGoogle Scholar | 24389329PubMed |
      (b) S. J. Woods, K. M. Hannan, R. B. Pearson, R. D. Hannan, Biochim. Biophys. Acta 2015, 1849, 821.
         | Crossref | GoogleScholarGoogle Scholar |

[10]  (a) P. M. Bruno, M. Lu, K. A. Dennis, H. Inman, C. J. Moore, J. Sheehe, S. J. Elledge, M. T. Hemann, J. R. Pritchard, Proc. Natl. Acad. Sci. USA 2020, 117, 4053.
         | Crossref | GoogleScholarGoogle Scholar | 32041867PubMed |
      (b) See also S. Yan, J. Xuan, N. Brajanovski, M. R. C. Tancock, P. B. Madhamshettiwar, K. J. Simpson, S. Ellis, J. Kang, C. Cullinane, K. E. Sheppard, K. M. Hannan, R. D. Hannan, E. Sanji, R. B. Pearson, K. T. Chen, Br. J. Cancer 2021, 124, 616.
         | Crossref | GoogleScholarGoogle Scholar |

[11]  (a) For some illustrative examples of the many applications of this technique, see: K. Shimokawa, K. Yamada, O. Ohno, Y. Oba, D. Umemura, Bioorg. Med. Chem. Lett. 2009, 19, 92.
         | Crossref | GoogleScholarGoogle Scholar | 19022665PubMed |
      (b) T. Takeuchi, N. Takahashi, K. Ishi, T. Kusayanagi, K. Kuramochi, F. Sugawara, Bioorg. Med. Chem. 2009, 17, 8113.
         | Crossref | GoogleScholarGoogle Scholar |
      (c) J. M. Chambers, L. M. Lindqvist, G. P. Savage, M. A. Rizzacasa, Bioorg. Med. Chem. Lett. 2016, 26, 262.
         | Crossref | GoogleScholarGoogle Scholar |
      (d) G. Zong, Z. Hu, S. O’Keefe, D. Tranter, M. J. Jannotti, L. Baron, B. Hall, K. Corfield, A. O. Paatero, M. J. Henderson, P. Roboti, J. Zhou, X. Sun, M. Govindarajan, J. M. Rohde, N. Blachard, R. Simmons, J. Inglese, Y. Du, C. Demangel, S. High, V. O. Paavilainen, W. Q. Shi, J. Am. Chem. Soc. 2019, 141, 8450.
         | Crossref | GoogleScholarGoogle Scholar |

[12]  For an overview of such possibilities, see: E. A. Specht, E. Braselmann, A. E. Palmer, Annu. Rev. Physiol. 2017, 79, 93.
         | Crossref | GoogleScholarGoogle Scholar | 27860833PubMed |

[13]  (a) R. Chinchilla, C. Nájera, Chem. Soc. Rev. 2011, 40, 5084.
         | Crossref | GoogleScholarGoogle Scholar | 21655588PubMed |
      (b) G. L. Larson, Synthesis 2018, 50, 2433.
         | Crossref | GoogleScholarGoogle Scholar |

[14]  I. V. Escamilla, L. F. R. Ramos, J. S. Escalera, A. A. Hernández, J. Mex. Chem. Soc. 2011, 55, 133.

[15]  L. Zhou, L. Xie, C. Liu, Y. Xiao, Chin. Chem. Lett. 2019, 30, 1799.
         | Crossref | GoogleScholarGoogle Scholar |

[16]  D. S. Tyler, J. Vappiani, T. Cañeque, E. Y. N. Lam, A. Ward, O. Gilan, Y.-C. Chan, A. Hienzsch, A. Rutkowska, T. Werner, A. J. Wagner, D. Lugo, R. Gregory, C. R. Molina, N. Garton, C. R. Wellaway, S. Jackson, L. MacPherson, M. Figueiredo, S. Stolzenburg, C. C. Bell, C. House, S.-H. Dawson, E. D. Hawkins, G. Drewes, R. K. Prinjha, R. Rodriguez, P. Ggandi, M. A. Dawson, Science 2017, 356, 1397.
         | Crossref | GoogleScholarGoogle Scholar | 28619718PubMed |

[17]  W. C. Still, M. Kahn, A. Mitra, J. Org. Chem. 1978, 43, 2923.
         | Crossref | GoogleScholarGoogle Scholar |

[18]  A. B. Pangborn, M. A. Giardello, R. H. Grubbs, R. K. Rosen, F. J. Timmers, Organometallics 1996, 15, 1518.
         | Crossref | GoogleScholarGoogle Scholar |

[19]  J. Pan, X. Wang, Y. Zhang, S. L. Buchwald, Org. Lett. 2011, 13, 4974.
         | Crossref | GoogleScholarGoogle Scholar | 21863838PubMed |

[20]  X. Huang, J. Tang, Tetrahedron 2003, 59, 4851.
         | Crossref | GoogleScholarGoogle Scholar |

[21]  A. W. Schwabacher, J. W. Lane, M. W. Schiesher, K. M. Leigh, C. W. Johnson, J. Org. Chem. 1998, 63, 1727.
         | Crossref | GoogleScholarGoogle Scholar |

[22]  L. Yuan, Z. Zhang, X. Xu, X. Zhou, Synth. Commun. 2014, 44, 1007.
         | Crossref | GoogleScholarGoogle Scholar |

[23]  N. Iranpoor, H. Firouzabadi, Gh. Ahhapour, A. R. Vaez zadeh, Tetrahedron 2002, 58, 8689.
         | Crossref | GoogleScholarGoogle Scholar |

[24]  G. M. Sheldrick, Acta Crystallogr. 2015, A71, 3.

[25]  O. V. Dolomanov, L. J. Bourhis, R. J. Gildea, J. A. K. Howard, H. Puschmann, J. Appl. Cryst. 2009, 42, 339.
         | Crossref | GoogleScholarGoogle Scholar |

[26]  G. M. Sheldrick, Acta Crystallogr. 2015, C71, 3.

[27]  N. Hein, D. P. Cameron, K. M. Hannan, N.-Y. N. Nguyen, C. Y. Fong, J. Sornkom, M. Wall, M. Pavy, C. Cullinane, J. Diesch, J. R. Devlin, A. J. George, E. Sanij, J. Quin, G. Poortinga, I. Verbrugge, A. Baker, D. Drygin, S. J. Harrison, J. D. Rozario, J. A. Powell, S. M. Pitson, J. Zuber, R. W. Johnstone, M. A. Dawson, M. A. Guthridge, A. Wei, G. A. McArthur, R. B. Pearson, R. D. Hannan, Blood 2017, 129, 2882.
         | Crossref | GoogleScholarGoogle Scholar | 28283481PubMed |