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RESEARCH FRONT
Contents Vol 65(7)

Copper(ii) and Palladium(ii) Complexes with Cytotoxic and Antibacterial Activity

Anwen M. Krause-Heuer A , Peter Leverett A , Albert Bolhuis B and Janice R. Aldrich-Wright A C
+ Author Affiliations
- Author Affiliations

A School of Science and Health, University of Western Sydney, Locked Bag 1797, Penrith South DC, NSW 2751, Australia.

B Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK.

C Corresponding author. Email: j.aldrich-wright@uws.edu.au

Australian Journal of Chemistry 65(7) 860-873 https://doi.org/10.1071/CH12058
Submitted: 31 January 2012  Accepted: 7 March 2012   Published: 9 May 2012

Abstract

The synthesis of eight square pyramidal copper complexes with general structure [Cu(IL)(AL)H2O]2+, where IL represents various methylated 1,10-phenanthrolines, and AL represents either 1S,2S- or 1R,2R-diaminocyclohexane, is reported, with the complexes synthesised as both the perchlorate and chloride salts. The crystal structures of [Cu(1,10-phenanthroline)(1S,2S-diaminocyclohexane](ClO4)2·H2O and [Cu(5,6-dimethyl-1,10-phenanthroline)(1S,2S-diaminocyclohexane](ClO4)2·1.5H2O are reported. Four square planar palladium complexes with general structure [Pd(IL)(AL)]Cl2 have also been synthesised. These complexes were synthesised in order to investigate the structure–activity relationship against both cancer cell lines and bacterial cultures. The copper complexes display anticancer activity similar to cisplatin and 1,10-phenanthroline (phen) in the L1210 murine leukaemia cell line. Methylation of the phen increased the copper complex cytotoxicity by approximately four-fold, compared with the non-methylated complex. No significant difference in activity was observed by altering the chirality of the diaminocyclohexane ligand. The copper complexes demonstrated antibacterial activity against Bacillus subtilis, Staphylococcus aureus, and Escherichia coli; however, high levels of toxicity (30–60 % of death) were observed in the nematode Caenorhabditis elegans. The copper complexes have also been shown to act as DNA nucleases, with the ability to cleave plasmid DNA in the presence of hydrogen peroxide. The palladium complexes all have half maximal inhibitory concentration (IC50) values of ~10 μM in the L1210 cell line, with no significant difference in the cytotoxicity of any of the compounds tested. Minimal antibacterial activity of the palladium complexes was observed.


References

[1]  A. Eastman, Cancer Cells 1990, 2, 275.
         | 1:CAS:528:DyaK3MXnsVGnsA%3D%3D&md5=b93c46656812eb7de49c39cca70bee59CAS |

[2]  S. L. Bruhn, J. H. Toney, S. J. Lippard, Prog. Inorg. Chem. 1990, 38, 477.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3MXktVSjsLc%3D&md5=3e4e9eb5f4045901f6a925cf7e6cbd6cCAS |

[3]  E. R. Jamieson, S. J. Lippard, Chem. Rev. 1999, 99, 2467.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXltV2lsrg%3D&md5=a3679d1cf3d9afc03d5d5444027322d2CAS |

[4]  B. Lippert, Cisplatin: Chemistry and Biochemistry of a Leading Anticancer Drug 1999 (Wiley-VCH: Weinheim).

[5]  M. V. Keck, S. J. Lippard, J. Am. Chem. Soc. 1992, 114, 3386.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38XhvVOmtbw%3D&md5=3d5844d6008022378cd7f0f86df7d306CAS |

[6]  L. F. Liu, J. C. Wang, Biochim. Biophys. Acta 1975, 395, 405.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE2MXkvFamtbs%3D&md5=0e778c8c162c55517c7f68f35e4e98e0CAS |

[7]  K. W. Jennette, J. T. Gill, J. A. Sadownick, S. J. Lippard, J. Am. Chem. Soc. 1976, 98, 6159.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE28XlslOhs7c%3D&md5=0b12a1402ce76ca1e8c9b7f9af1a720dCAS |

[8]  N. J. Wheate, R. I. Taleb, A. M. Krause-Heuer, R. L. Cook, S. Wang, V. J. Higgins, J. R. Aldrich-Wright, Dalton Trans. 2007, 5055,
         | Crossref | GoogleScholarGoogle Scholar |

[9]  A. M. Krause-Heuer, R. Grünert, S. Kühne, M. Buczkowska, N. J. Wheate, D. D. L. Pevelen, L. R. Boag, D. M. Fisher, J. Kasparkova, J. Malina, P. J. Bednarski, V. Brabec, J. R. Aldrich-Wright, J. Med. Chem. 2009, 52, 5474.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXpsFarsL8%3D&md5=07303ba6f9c96f2877ffb5abdba67940CAS |

[10]  K. B. Garbutcheon-Singh, M. P. Grant, B. W. Harper, A. M. Krause-Heuer, M. Manohar, N. Orkey, J. R. Aldrich-Wright, Curr. Top. Med. Chem. 2011, 11, 521.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXktVOqsrw%3D&md5=26a8e14413b2c8a56e68e6b5db791f72CAS |

[11]  L. E. Marshall, D. R. Graham, K. A. Reich, D. S. Sigman, Biochemistry 1981, 20, 244.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL3MXmtVSiug%3D%3D&md5=a542e9aecff64886d694e50123312892CAS |

[12]  K. Takamiya, Nature 1960, 185, 190.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF3cXot1WrtQ%3D%3D&md5=57797965cfd8cf84fbf80481b63a225fCAS |

[13]  D. S. Sigman, D. R. Graham, V. D’Aurora, A. M. Stern, J. Biol. Chem. 1979, 254, 12269.
         | 1:CAS:528:DyaL3cXitlWg&md5=ec958679962b318618480f9f1b81868fCAS |

[14]  T. J. Dwyer, B. H. Geierstanger, M. Mrksich, P. B. Dervan, D. E. Wemmer, J. Am. Chem. Soc. 1993, 115, 9900.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXhtlGjt7k%3D&md5=7b6edebcc7e367afc3ee608b85f0148dCAS |

[15]  B. C. Bales, M. Pitié, B. Meunier, M. M. Greenberg, J. Am. Chem. Soc. 2002, 124, 9062.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XltFOjsbY%3D&md5=e50571feac65d35ba4a0bd30c49da1a1CAS |

[16]  M. Pitié, C. J. Burrows, B. Meunier, Nucleic Acids Res. 2000, 28, 4856.
         | Crossref | GoogleScholarGoogle Scholar |

[17]  J. M. C. Gutteridge, B. Halliwell, Biochem. Pharmacol. 1982, 31, 2801.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL38XlslOiurs%3D&md5=4d54ea071985cee4a6a7841271729a9cCAS |

[18]  S. Dhar, A. R. Chakravarty, Inorg. Chem. 2003, 42, 2483.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXitF2ru7s%3D&md5=c140e19fde10a08b5ccd93c2b5b1c3d1CAS |

[19]  S. Dhar, M. Nethaji, A. R. Chakravarty, Inorg. Chem. 2006, 45, 11043.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xht1KqsL3M&md5=12c45808078c795a55297905f0da60bdCAS |

[20]  L.-P. Lu, M.-L. Zhu, P Yang, J. Inorg. Biochem. 2003, 95, 31.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXivFSjs7Y%3D&md5=cecb4032a3d86a9242d1b7e67f4443bfCAS |

[21]  S. Tardito, L. Marchio, Curr. Med. Chem. 2009, 16, 1325.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXltVeqsbs%3D&md5=9996ffc0599472164ab2f6b115708826CAS |

[22]  C. Marzano, M. Pellei, F. Tisato, C. Santini, Anti-Cancer Agent Med. Chem. 2009, 9, 185.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXjvVOmsL0%3D&md5=5981b2ac7f422632ba50b0ddb1c16ff9CAS |

[23]  J. L. García-Giménez, M. González-Álvarez, M. Liu-González, B. Macías, J. Borrás, G. Alzuet, J. Inorg. Biochem. 2009, 103, 923.
         | Crossref | GoogleScholarGoogle Scholar |

[24]  S. Zhang, Y. Zhu, C. Tu, H. Wei, Z. Yang, L. Lin, J. Ding, J. Zhang, Z. Guo, J. Inorg. Biochem. 2004, 98, 2099.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXpslGntro%3D&md5=0959133fe398945da45addd48c4a5a41CAS |

[25]  I. Gracia-Mora, L. Ruiz-Ramirez, C. Gomez-Ruiz, M. Tinoco-Mendez, A. Marquez-Quinones, L. R.-D. Lira, A. Marin-Hernandez, L. Macias-Rosales, M. E. Bravo-Gomez, Met. Based Drugs 2001, 8, 19.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXlt1KqtbY%3D&md5=0af5129b1a1ea49ad5d2f18cddeff162CAS |

[26]  A. De Vizcaya-Ruiz, A. Rivero-Müller, L. Ruiz-Ramirez, G. E. N. Kass, L. R. Kelland, R. M. Orr, M. Dobrota, Toxicol. In Vitro 2000, 14, 1.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXhsVWkur8%3D&md5=d183b51d42b7ca698c6b65d3061e7495CAS |

[27]  A. De Vizcaya-Ruiz, A. Rivero-Müller, L. Ruiz-Ramirez, J. A. Howarth, M. Dobrota, Toxicology 2003, 194, 103.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXptVGrtb4%3D&md5=306ec4eaf577f999ab76a21f0b6edcfdCAS |

[28]  E. K. Efthimiadou, M. E. Katsarou, A. Karaliota, G. Psomas, J. Inorg. Biochem. 2008, 102, 910.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXjtlCntL4%3D&md5=de67dad45e9fa364281f6b144674501cCAS |

[29]  E. K. Efthimiadou, Y. Sanakis, C. P. Raptopoulou, A. Karaliota, N. Katsaros, G. Psomas, Bioorg. Med. Chem. 2006, 16, 3864.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XlsVyrsrw%3D&md5=a3f35d3ea3ffbd7aa9881691c5b27b6eCAS |

[30]  G. Psomas, A. Tarushi, E. K. Efthimiadou, Y. Sanakis, C. P. Raptopoulou, N. Katsaros, J. Inorg. Biochem. 2006, 100, 1764.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtVyisLjJ&md5=ac9e3d0f9906f4cb4c5d45e6db5d948cCAS |

[31]  E. K. Efthimiadou, Y. Sanakis, M. Katsarou, C. P. Raptopoulou, A. Karaliota, N. Katsaros, G. Psomas, J. Inorg. Biochem. 2006, 100, 1378.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xmslykt7g%3D&md5=a2f9c6c6052cebb6e3c76a3349d70e5dCAS |

[32]  M. E. Katsarou, E. K. Efthimiadou, G. Psomas, A. Karaliota, D. Vourloumis, J. Med. Chem. 2008, 51, 470.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXot1Crtg%3D%3D&md5=ad2c46986f669716fd125818e11aa1f6CAS |

[33]  P. Gameiro, C. Rodrigues, T. Baptista, I. Sousa, B. de Castro, Int. J. Pharm. 2007, 334, 129.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXjtVantr4%3D&md5=d7c9630301536a812f1737e921e03b59CAS |

[34]  E. Gao, C. Liu, M. Zhu, H. Lin, Q. Wu, L. Liu, Anti-Cancer Agent Med. Chem. 2009, 9, 356.
         | 1:CAS:528:DC%2BD1MXks1Cnsr8%3D&md5=3dec43c5d89f394246ca12595bf827c1CAS |

[35]  A. C. F. Caires, Anti-Cancer Agent Med. Chem. 2007, 7, 484.
         | 1:CAS:528:DC%2BD2sXhtV2gtr3N&md5=7760bafa611734ac6144867591c72369CAS |

[36]  K. H. Puthraya, T. S. Srivastava, J. Inorg. Biochem. 1985, 25, 207.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL28XksFCisw%3D%3D&md5=d4768334f1e329e420fd6dad4a8b2914CAS |

[37]  R. Mital, G. M. Shah, T. S. Srivastava, R. K. Bhattacharya, Life Sci. 1992, 50, 781.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38Xks1ahur8%3D&md5=46688583f30095cab328e0398c2c5c8eCAS |

[38]  G. M. Sheldrick, Acta Crystallogr. 2008, 112,
         | Crossref | GoogleScholarGoogle Scholar |

[39]  A. W. Bauer, W. M. Kirby, J. C. Sherris, M. Turck, Am. J. Clin. Pathol. 1966, 45, 493.
         | 1:STN:280:DyaF287htV2isA%3D%3D&md5=b48041247e4abe68bfb486370acbdd7eCAS |

[40]  J. E. Peters, T. E. Thate, N. L. Craig, J. Bacteriol. 2003, 185, 2017.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXitFWktb4%3D&md5=d17f2787c686183f3b450b5ed78fc53cCAS |

[41]  F. Kunst, N. Ogasawara, I. Moszer, A. M. Albertini, G. Alloni, V. Azevedo, M. G. Bertero, P. Bessieres, A. Bolotin, S. Borchert, R. Borriss, L. Boursier, A. Brans, M. Braun, S. C. Brignell, S. Bron, S. Brouillet, C. V. Bruschi, B. Caldwell, V. Capuano, N. M. Carter, S. K. Choi, J. J. Codani, I. F. Connerton, N. J. Cummings, R. A. Daniel, F. Denizot, K. M. Devine, A. Dusterhoft, S. D. Ehrlich, P. T. Emmerson, K. D. Entian, J. Errington, C. Fabret, E. Ferrari, D. Foulger, C. Fritz, M. Fujita, Y. Fujita, S. Fuma, A. Galizzi, N. Galleron, S. Y. Ghim, P. Glaser, A. Goffeau, E. J. Golightly, G. Grandi, G. Guiseppi, B. J. Guy, K. Haga, J. Haiech, C. R. Harwood, A. Henaut, H. Hilbert, S. Holsappel, S. Hosono, M. F. Hullo, M. Itaya, L. Jones, B. Joris, D. Karamata, Y. Kasahara, M. Klaerr-Blanchard, C. Klein, Y. Kobayashi, P. Koetter, G. Koningstein, S. Krogh, M. Kumano, K. Kurita, A. Lapidus, S. Lardinois, J. Lauber, V. Lazarevic, S. M. Lee, A. Levine, H. Liu, S. Masuda, C. Mauel, C. Medigue, N. Medina, R. P. Mellado, M. Mizuno, D. Moestl, S. Nakai, M. Noback, D. Noone, M. O’Reilly, K. Ogawa, A. Ogiwara, B. Oudega, S. H. Park, V. Parro, T. M. Pohl, D. Portetelle, S. Porwollik, A. M. Prescott, E. Presecan, P. Pujic, B. Purnelle, G. Rapoport, M. Rey, S. Reynolds, M. Rieger, C. Rivolta, E. Rocha, B. Roche, M. Rose, Y. Sadaie, T. Sato, E. Scanlan, S. Schleich, R. Schroeter, F. Scoffone, J. Sekiguchi, A. Sekowska, S. J. Seror, P. Serror, B. S. Shin, B. Soldo, A. Sorokin, E. Tacconi, T. Takagi, H. Takahashi, K. Takemaru, M. Takeuchi, A. Tamakoshi, T. Tanaka, P. Terpstra, A. Tognoni, V. Tosato, S. Uchiyama, M. Vandenbol, F. Vannier, A. Vassarotti, A. Viari, R. Wambutt, E. Wedler, H. Wedler, T. Weitzenegger, P. Winters, A. Wipat, H. Yamamoto, K. Yamane, K. Yasumoto, K. Yata, K. Yoshida, H. F. Yoshikawa, E. Zumstein, H. Yoshikawa, A. Danchin, Nature 1997, 390, 249.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXnsVyqtrY%3D&md5=098da40220360b062f03453d215798bfCAS |

[42]  A. E. van Merode, H. C. van der Mei, H. J. Busscher, K. Waar, B. P. Krom, Microbiology 2006, 152, 807.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XjtVOlu74%3D&md5=8164a55bf7a2b61e411db1fc20118945CAS |

[43]  E. J. Feil, J. E. Cooper, H. Grundmann, D. A. Robinson, M. C. Enright, T. Berendt, S. J. Peacock, J. M. Smith, M. Murphy, B. G. Spratt, C. E. Moore, N. P. Day, J. Bacteriol. 2003, 185, 3307.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXkt1Sgtbc%3D&md5=bd753b931fcc465791aeea7a9fd5f6efCAS |

[44]  J. M. Andrews, J. Antimicrob. Chemother. 2001, 48, 5.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXlsVegtr8%3D&md5=ee1c2227a297eb8ef7c98438a5824967CAS |

[45]  T. I. Moy, A. R. Ball, Z. Anklesaria, G. Casadei, K. Lewis, F. M. Ausubel, Proc. Natl. Acad. Sci. USA 2006, 103, 10414.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xntl2qu7Y%3D&md5=24371a0260490c91cccb4d28555d682aCAS |

[46]  A. Bolhuis, L. Hand, J. E. Marshall, A. D. Richards, A. Rodger, J. Aldrich-Wright, Eur. J. Pharm. Sci. 2011, 42, 313.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXjsFChtrc%3D&md5=d4a5f419387fe1fd8f2a7c82569c0fc4CAS |

[47]  S. Tardito, I. Bassanetti, C. Bignardi, L. Elviri, M. Tegoni, C. Mucchino, O. Bussolati, R. Franchi-Gazzola, L. Marchiò, J. Am. Chem. Soc. 2011, 133, 6235.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXktFSrtbs%3D&md5=8d82adc65dc2a0f19beefda6a654cd8eCAS |

[48]  M. Pitié, A. Croisy, D. Carrez, C. Boldron, B. Meunier, ChemBioChem 2005, 6, 686.
         | Crossref | GoogleScholarGoogle Scholar |

[49]  D. M. Fisher, R. R. Fenton, J. R. Aldrich-Wright, Chem. Commun. 2008, 5613,
         | Crossref | GoogleScholarGoogle Scholar |

[50]  K. B. Garbutcheon-Singh, Honours Thesis 2008, University of Western Sydney.

[51]  D. M. Fisher, P. J. Bednarski, R. Grunert, P. Turner, R. R. Fenton, J. R. Aldrich-Wright, ChemMedChem 2007, 2, 488.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXkvV2jtrs%3D&md5=d558d5ba4bfa40dd3e141b68e01f0581CAS |

[52]  S. Kemp, N. J. Wheate, M. J. Pisani, J. R. Aldrich-Wright, J. Med. Chem. 2008, 51, 2787.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXks1OntL4%3D&md5=ad70e3b33bd64d0fe4bf72aabdc27e4aCAS |

[53]  B. J. Corden, Inorg. Chim. Acta 1987, 137, 125.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2sXlvVCntL4%3D&md5=7f2eedef6b4612bd0bf7c31f54d3b73bCAS |

[54]  D. O’Callaghan, A. Vergunst, Curr. Opin. Microbiol. 2010, 13, 79.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhs1OgtrY%3D&md5=06786dfb6ffe2364e52abab8c7ec072cCAS |

[55]  C. D. Sifri, J. Begun, F. M. Ausubel, S. B. Calderwood, Infect. Immun. 2003, 71, 2208.
         | Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXislOhtL4%3D&md5=dd25bd42218cc5bb500c98efc5e953e2CAS |