Synthesis and Characterisation of RuII Polypyridyl Complexes: DNA-Binding, Photocleavage, and Topoisomerase I and II Inhibitory Activity
Xiaojun He A C , Guang Yang A C , Xiaonan Sun A , Lingjun Xie A and Lifeng Tan A B DA College of Chemistry, Xiangtan University, Xiangtan 411105, China.
B Key Lab of Environment-friendly Chemistry and Application in Ministry of Education, Xiangtan University, Xiangtan 411105, China.
C These two authors are both first authors.
D Corresponding author. Email: lfwyxh@yahoo.com.cn
Australian Journal of Chemistry 66(11) 1406-1414 https://doi.org/10.1071/CH13329
Submitted: 27 June 2013 Accepted: 23 July 2013 Published: 20 August 2013
Abstract
Two mixed-ligand ruthenium(ii) complexes [Ru(phen)2(cptcp)]2+ (Ru1; phen = 1,10-phenanthroline, cptcp = 2-(4-carbazol-9-yl-phenyl)-1H-1,3,7,8-tetraaza-cyclopenta-[l]-phenanthrene) and [Ru(phen)2(btcpc)]2+ (Ru2; btcpc = 9-butyl-6-(1H-1,3,7,8-tetraaza-cyclo-cyclopenta-[l]-phenanthren-2-yl)-9H-carbazole-3-carbaldehyde) have been synthesised and characterised. The DNA-binding behaviours of the two complexes have been investigated by using spectroscopic and viscosity measurements. Results suggest that the two complexes bind to DNA by intercalation. The photocleavage of plasmid pBR322 DNA indicates that Ru1 exhibits more effective DNA cleavage activity in comparison to that exhibited by Ru2 under the same conditions, and different cleavage mechanisms are determined. Topoisomerase inhibition and DNA strand passage assay confirm that Ru1 may act as an efficient dual inhibitor of topoisomerases I and II, whereas Ru2 may only act as a single inhibitor of topoisomerases II.
References
[1] (a) J. M. Berger, S. J. Gamblin, S. C. Harrison, J. C. Wang, Nature 1996, 379, 225.| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28Xmtl2gsg%3D%3D&md5=c8b1e7114246112d33f3c22430789e23CAS | 8538787PubMed |
(b) J. C. Wang, Annu. Rev. Biochem. 1996, 65, 635.
| Crossref | GoogleScholarGoogle Scholar |
[2] (a) A. Y. Chen, L. F. Liu, Annu. Rev. Pharmacol. Toxicol. 1994, 34, 191.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2cXmt1Sks74%3D&md5=3931baa6e48e1130e4fe73f59571d5acCAS | 8042851PubMed |
(b) J. J. Champoux, Annu. Rev. Biochem. 2001, 70, 369.
| Crossref | GoogleScholarGoogle Scholar |
[3] J. C. Wang, Nat. Rev. Mol. Cell Biol. 2002, 3, 430.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XltlartLw%3D&md5=282b067a07911c51dbab0506fce8cc74CAS | 12042765PubMed |
[4] S. Salerno, F. D. Settimo, S. Taliani, F. Simorini, C. L. Motta, G. Fornaciari, A. M. Marini, Curr. Med. Chem. 2010, 17, 4270.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXhs1artr%2FI&md5=ec6eff3889a7a45ab3c56131547de768CAS | 20939813PubMed |
[5] (a) J. A. Holden, Curr. Med. Chem. 2001, 1, 1.
| 1:CAS:528:DC%2BD3MXktlShsbY%3D&md5=9116d14385c9171d28bf9a69f1531797CAS |
(b) J. L. Nitiss, Nat. Rev. Cancer 2009, 9, 338.
| Crossref | GoogleScholarGoogle Scholar |
[6] (a) H. K. Wang, S. L. Morris-Natschke, K. H. Lee, Med. Res. Rev. 1997, 17, 367.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXks1Oit7k%3D&md5=3a2b8d044f14a8ba5a594500610c047dCAS | 9211397PubMed |
(b) D. F. Kehrer, O. Soepenberg, W. J. Loos, J. Verweij, A. Sparreboom, Anticancer Drugs 2001, 12, 89.
| Crossref | GoogleScholarGoogle Scholar |
(c) H. Jensen, A. V. Thougaard, M. Grauslund, B. Søkilde, E. V. Carstensen, H. K. Dvinge, D. A. Scudiero, P. B. Jensen, R. H. Shoemaker, M. Sehested, Cancer Res. 2005, 65, 7470.
| Crossref | GoogleScholarGoogle Scholar |
(d) N. Dias, H. Vezin, A. Lansiaux, C. Bailly, Top. Curr. Chem. 2005, 253, 89.
(e) A. Morrell, M. Placzek, S. Parmley, S. Antony, T. S. Dexheimer, Y. Pommier, M. Cushman, J. Med. Chem. 2007, 50, 4419.
| Crossref | GoogleScholarGoogle Scholar |
(f) R. Gaur, L. Mishra, Inorg. Chem. 2012, 51, 3059.
| Crossref | GoogleScholarGoogle Scholar |
[7] (a) M. Chandra, A. N. Sahay, D. S. Pandey, R. P. Tripathi, J. K. Saxena, V. J. M. Reddy, M. C. Puerta, P. J. Valerga, J. Organomet. Chem. 2004, 689, 2256.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXksVeqsLs%3D&md5=95780d36bb23eb137c8d139ded984087CAS |
(b) S. K. Singh, S. Joshi, A. R. Singh, J. K. Saxena, D. S. Pandey, Inorg. Chem. 2007, 46, 10869.
| Crossref | GoogleScholarGoogle Scholar |
(c) X. Chen, F. Gao, W. Y. Yang, J. Sun, Z. X. Zhou, L. N. Ji, Inorg. Chim. Acta 2011, 378, 140.
| Crossref | GoogleScholarGoogle Scholar |
(d) Y. C. Lo, T. P. Ko, W. C. Su, T. L. Su, A. H. Wang, J. Inorg. Biochem. 2009, 103, 1082.
| Crossref | GoogleScholarGoogle Scholar |
(e) X. Chen, F. Gao, Z. X. Zhou, W. Y. Yang, L. T. Guo, L. N. Ji, J. Inorg. Biochem. 2010, 104, 576.
| Crossref | GoogleScholarGoogle Scholar |
[8] (a) B. M. Zeglis, V. C. Pierrea, J. K. Barton, Chem. Commun. 2007, 44, 4565.
| Crossref | GoogleScholarGoogle Scholar |
(b) C. A. Puckett, R. J. Erns, J. K. Barton, Dalton Trans. 2010, 39, 1159.
| Crossref | GoogleScholarGoogle Scholar |
(c) M. R. Gill, J. A. Thomas, Chem. Soc. Rev. 2012, 41, 3179.
| Crossref | GoogleScholarGoogle Scholar |
[9] (a) W. A. Denny, Expert Opin. Investig. Drugs 1997, 6, 1845.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXnvFGntrg%3D&md5=7aec4e93112bf8a8092cb918a09eaa41CAS | 15989585PubMed |
(b) T. Simon, A. Langler, F. Berthold, T. Klingebiel, B. Hero, J. Pediatr. Hematol. Oncol. 2007, 29, 101.
| Crossref | GoogleScholarGoogle Scholar |
(c) H. J. Choi, B. C. Cho, S. J. Shin, S. H. Cheon, J. Y. Jung, J. Chang, S. K. Kim, J. H. Sohn, J. H. Kim, Cancer Chemother. Pharmacol. 2008, 61, 309.
| Crossref | GoogleScholarGoogle Scholar |
(d) B. Saraiya, M. Gounder, J. Dutta, A. Saleem, C. Collazo, L. Zimmerman, A. Nazar, M. Gharibo, D. Schaar, Y. Lin, W. Shih, J. Aisner, R. K. Strai, E. H. Rubin, Anticancer Drugs 2008, 19, 411.
| Crossref | GoogleScholarGoogle Scholar |
[10] (a) F. Gao, H. Chao, J. Q. Wang, Y. X. Yuan, B. Sun, Y. F. Wei, B. Pen, L. N. Ji, J. Biol. Inorg. Chem. 2007, 12, 1015.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXpvVagtL4%3D&md5=f6ed0580ffa06047439b00c8ccb3bcc9CAS | 17659367PubMed |
(b) S. Sharma, S. K. Singh, D. S. Pandey, Inorg. Chem. 2008, 47, 1179.
| Crossref | GoogleScholarGoogle Scholar |
(c) F. Gao, H. Chao, F. Zhou, X. Chen, Y. F. Wei, K. Z. Zheng, L. N. Ji, J. Inorg. Biochem. 2008, 102, 1050.
| Crossref | GoogleScholarGoogle Scholar |
(d) P. Kumar, A. K. Singh, J. K. Saxena, D. S. Pandey, J. Organomet. Chem. 2009, 694, 3570.
| Crossref | GoogleScholarGoogle Scholar |
[11] J. F. Kou, C. Qian, J. Q. Wang, X. Chen, L. L. Wang, H. Chao, L. N. Ji, J. Biol. Inorg. Chem. 2012, 17, 81.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtVCqt7vF&md5=1e37a51ee7b308f8ec3da485cdc0a973CAS | 21858685PubMed |
[12] E. A. Steck, A. R. Day, J. Am. Chem. Soc. 1943, 65, 452.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaH3sXhsVGisg%3D%3D&md5=707260f85cc550ae19a653b6e26b4674CAS |
[13] J. G. Liu, Q. L. Zhan, L. N. Ji, Transit. Metal Chem. 2001, 26, 733.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXosV2iu7k%3D&md5=25683399a45aa729905d0d4203ecdcb2CAS |
[14] J. Z. Wu, B. H. Ye, L. Wang, L. N. Ji, J. Y. Zhou, R. H. Li, Z. Y. Zhou, J. Chem. Soc., Dalton Trans. 1997, 8, 1395.
| Crossref | GoogleScholarGoogle Scholar |
[15] L. F. Tan, J. L. Shen, J. Liu, L. L. Zeng, L. H. Jin, C. Weng, Dalton Trans. 2012, 41, 4575.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XktFert78%3D&md5=59b07b1536282dc1141f982fd999d80dCAS |
[16] F. Gao, H. Chao, F. Zhou, Y. X. Yuan, B. Peng, L. N. Ji, J. Inorg. Biochem. 2006, 100, 1487.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xot1Wrs78%3D&md5=5b201d9247f0b5766d200cd25046dfa2CAS | 16766033PubMed |
[17] J. G. Liu, Q. L. Zhang, X. F. Shi, L. N. Ji, Inorg. Chem. 2001, 40, 5045.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXls12qtLs%3D&md5=8895ea8693f1c10432074e3cd58db2f8CAS | 11531457PubMed |
[18] J. B. Lepecq, C. Paoletti, J. Mol. Biol. 1967, 27, 87.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF2sXksFSns7c%3D&md5=6ca666d50b5fb68116f9abe1841aabe0CAS | 6033613PubMed |
[19] J. L. Morgan, D. P. Buck, A. G. Turley, J. G. Collins, F. R. Keene, Inorg. Chim. Acta 2006, 359, 888.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XlvVyrsQ%3D%3D&md5=60dbb4e54760d0db44b7f4ae1195de3cCAS |
[20] S. Shi, J. Zhao, X. T. Geng, T. M. Yao, H. L. Huang, T. L. Liu, L. F. Zheng, Z. H. Liu, D. J. Yang, L. N. Ji, Dalton Trans. 2010, 39, 2490.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXitlent7k%3D&md5=dfe0118fbf66d89278cd5741a255a2adCAS | 20179840PubMed |
[21] S. Satyanarayana, J. C. Dabroniak, J. B. Chaires, Biochemistry 1992, 31, 9319.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38Xls1Kjtbc%3D&md5=4d7d30159cd253ce3aa9d73ef9035059CAS | 1390718PubMed |
[22] E. Tselepi-Kalouli, N. Katsaros, J. Inorg. Biochem. 1989, 37, 271.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3cXnt1Cgug%3D%3D&md5=fd2e7325b7467917677610f5fb87c3daCAS | 2628546PubMed |
[23] (a) J. Waring, J. Mol. Biol. 1965, 13, 269.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF2MXks1Cmuro%3D&md5=4112852f3d5f62fc5da85a42db4d5ddfCAS |
(b) G. A. Neyhart, N. Grover, S. R. Smith, W. A. Kalsbeck, T. A. Fairly, M. Cory, H. H. Thorp, J. Am. Chem. Soc. 1993, 115, 4423.
| Crossref | GoogleScholarGoogle Scholar |
(c) S. Shi, T. Xie, T. M. Yao, C. R. Wang, X. T. Geng, D. J. Yang, L. J. Han, L. N. Ji, Polyhedron 2009, 28, 1355.
| Crossref | GoogleScholarGoogle Scholar |
[24] J. K. Barton, A. L. Raphael, J. Am. Chem. Soc. 1984, 106, 2466.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL2cXitVGrsb8%3D&md5=0439f7443c7d5778b57bb9136191518dCAS |
[25] G. Cohen, H. Eisenberg, Biopolymers 1969, 8, 45.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF1MXltV2jtbY%3D&md5=01e7fab4bb60274507aa6c3db20a59d5CAS |
[26] H. Y. Mei, J. K. Barton, Proc. Natl. Acad. Sci. USA 1988, 85, 1339.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1cXitVWjs7c%3D&md5=47efe26b5253db6b4553dab7f5d619d5CAS | 3422737PubMed |
[27] J. M. Fortune, L. Velea, D. E. Graves, T. Utsugi, Y. Yamada, N. Osheroff, Biochemistry 1999, 38, 15580.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXmvFKqtb0%3D&md5=d87c9f0f47484121da08008d85e1c7baCAS | 10569942PubMed |
[28] K. J. Du, J. Q. Wang, J. F. Kou, G. Y. Li, L. L. Wang, H. Chao, L. N. Ji, Eur. J. Med. Chem. 2011, 46, 1056.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXjsFWhsbg%3D&md5=85694213019b82538a96b19f5625c854CAS | 21295892PubMed |
[29] M. Yamada, Y. Tanaka, Y. Yoshimato, S. Kuroda, I. Shimao, Bull. Chem. Soc. Jpn. 1992, 65, 1006.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38XktVOru7s%3D&md5=d937a72895eed9ed34b516b3d7a1372cCAS |
[30] B. P. Sullivan, D. J. Salmon, T. J. Meyer, Inorg. Chem. 1978, 17, 3334.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE1cXmtVyhtbw%3D&md5=657d4669f461b9f639416e1af476aa3dCAS |
[31] X. M. Wang, Y. F. Zhou, W. T. Yu, C. Wang, Q. Fang, M. H. Jiang, H. Lei, H. Z. Wang, J. Mater. Chem. 2000, 10, 2698.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXot1Kkt7c%3D&md5=8aba4596b599b83d7faaf0a17a3d1791CAS |
[32] J. Marmur, J. Mol. Biol. 1961, 3, 208.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaF3MXosl2kuw%3D%3D&md5=0b1641b6b52762892b9e98f5f4da94a0CAS |
[33] M. F. Reichmann, S. A. Rice, C. A. Thomas, P. Doty, J. Am. Chem. Soc. 1954, 76, 3047.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaG2cXmtVKmsg%3D%3D&md5=51517624e34ac257bdf5ffea04cf1ba6CAS |
[34] M. T. Carter, M. Rodriguez, A. Bard, J. Am. Chem. Soc. 1989, 111, 8901.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaL1MXmt1Shtrk%3D&md5=3b02b4ea30e09440c755e71af07f7811CAS |
[35] N. Osheroff, E. R. Shelton, D. L. Brutlag, J. Biol. Chem. 1983, 258, 9536.
| 1:CAS:528:DyaL3sXltVWnt7Y%3D&md5=a1a4f6666db40d3bb641384253524568CAS | 6308011PubMed |
[36] J. M. Fortune, N. Osheroff, J. Biol. Chem. 1998, 273, 17643.
| Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXkvFarsLs%3D&md5=1d2d2b6f4ff16e3bfc9fca52cb960112CAS | 9651360PubMed |