DNA Binding Properties and Cytotoxic Activities of Two Trinuclear Ruthenium(Ⅱ) Polypyridyl Complexes

doi:10.1007/s40242-014-3560-x

Chemical Research in Chinese Universities ›› 2014, Vol. 30 ›› Issue (3): 461-467.doi: 10.1007/s40242-014-3560-x

Previous Articles Next Articles

DNA Binding Properties and Cytotoxic Activities of Two Trinuclear Ruthenium(Ⅱ) Polypyridyl Complexes

XU Li¹, CHEN Yu², WEI Hui¹, WU Wenshan¹, LI Zhongzhi¹, LIN Yiwei¹, CHAO Hui³, JI Liangnian³

1. School of Chemistry and Chemical Engineering, Guangdong Pharmaceutical University, Zhongshan 528458, P. R. China;
2. State Key Laboratory of Biocontrol, Department of Biochemistry, College of Life Sciences, Sun Yat-sen University, Guangzhou 510006, P. R. China;
3. School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, P. R. China

Received:2013-12-20 Revised:2014-02-11 Online:2014-06-01 Published:2014-03-05
Contact: XU Li E-mail:xuli473@163.com
Supported by:
Supported by the National Natural Science Foundation of China(No.21301034) and the Natural Science Foundation of Guangdong Province, China(No.S2013040014083).

Abstract

Abstract:

The interactions between two trinuclear Ru(Ⅱ) complexes and calf thymus DNA(CT DNA) were studied via absorption spectroscopy, reverse salt titrations, binding stoichiometry, DNA melting experiments, as well as viscosity measurement. The results indicate that complexes 1 and 2 bind to DNA via the interaction of the planar π-delocalized system of the complexes with intrinsic binding constants of 4.18×10⁵ and 3.85×10⁶ L/mol, respectively, and non-electrostatic binding free energy makes a predominant contribution to the binding free energy. The in vitro cytotoxic activity of complexes 1 and 2 was evaluated by the MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl- 2H-tetrazolium bromide] method. Complex 1 shows higher anticancer potency than complex 2 against four tumor cell lines. Further mechanism study indicates that complexes 1 and 2 can cause cell cycle arrest in the G₂/M phase.

Key words: Ruthenium(Ⅱ) complex, DNA binding, Cell cycle

XU Li, CHEN Yu, WEI Hui, WU Wenshan, LI Zhongzhi, LIN Yiwei, CHAO Hui, JI Liangnian. DNA Binding Properties and Cytotoxic Activities of Two Trinuclear Ruthenium(Ⅱ) Polypyridyl Complexes[J]. Chemical Research in Chinese Universities, 2014, 30(3): 461-467.

References

[1] Chen G. J., Qiao X., Qiao P. Q., Xu G. J., Xu J. Y., Tian J. L., Gu W., Liu X., Yan S. P., J. Inorg. Biochem., 2011, 105, 119
[2] Zuber G., Quada J. C., Hecht S. M., J. Am. Chem. Soc., 1998, 120, 9368
[3] Barve A., Kumbhar A., Bhat M., Joshi B., Butcher R., Sonawane U., Joshi R., Inorg. Chem., 2009, 48, 9120
[4] Bruijnincx P. C., Sadler P. J., Curr. Opin. Chem. Biol., 2008, 12, 197
[5] Kostova I., Curr. Med. Chem., 2006, 13, 1085
[6] Antonarakis E. S., Emadi A., Cancer Chemother. Pharmacol., 2010, 66, 1
[7] Ang W. H., Dyson P. J., Eur. J. Inorg. Chem., 2006, 20, 4003
[8] Tan C. P., Lai S. S., Wu S. H., Hu S., Zhou L. J., Chen Y., Wang M. X., Zhu Y. P., Lian W., Peng W. L., Ji L. N., Xu A. L., J. Med. Chem., 2010, 53, 7613
[9] Schatzschneider U., Niesel J., Ott I., Gust R., Alborzinia H., Wolfl S., ChemMedChem, 2008, 3, 1104
[10] Barragán F., López-Senín P., Salassa L., Betanzos-Lara S., Habtemariam A., Moreno V., Sadler P. J., Marchán V., J. Am. Chem. Soc., 2011, 133, 14098
[11] Sun Y., Ojaimi M. E., Hammitt R., Thummel R. P., Turro C., J. Phys. Chem. B, 2010, 114, 14664
[12] Rademaker-Lakhai J. M., van den Bongard D., Pluim D., Beijnen J. H., Schellens J. H. M., Clin. Cancer Res., 2004, 10, 3717
[13] Hartinger C. G., Jakupec M. A., Zorbas-Seifried S., Groessl M., Egger A., Berger W., Zorbas H., Dyson P. J., Keppler B. K., Chem. Biodiversity, 2008, 5, 2140
[14] Norden B., Lincoln P., Akerman B., Tuite E., Metal Ions in Biological System: Probing of Nucleic Acids by Metal Ion Complexes of Small Molecules, Mercel Dekker, New York, 1996, 177
[15] Choi S. D., Kim M. S., Kim S. K., Lincoln P., Tuite E., Nordén B., Biochemistry, 1997, 36, 214
[16] Keene F. R., Smith J. A., Collins J. G., Coord. Chem. Rev., 2009, 253, 2021
[17] Rajput C., Rutkaite R., Swanson L., Haq I., Thomas J. A., Chem. Eur. J., 2006, 12, 4611
[18] Nordell P., Westerlund F., Wilhelmsson L. M., Nordén B., Lincoln P., Angew. Chem. Int. Ed., 2007, 46, 2203
[19] Xu L., Liao G. L., Chen X., Zhao C. Y., Chao H., Ji L. N., Inorg. Chem. Commun., 2010, 13, 1050
[20] Marmur J., J. Mol. Biol., 1961, 3, 208
[21] Reichmann M. E., Rice S. A., Thomas C. A., Doty P., J. Am. Chem. Soc., 1954, 76, 3047
[22] Wolf A., Shimer G. H. Jr., Meehan T., Biochemistry, 1987, 26, 6392
[23] Chaires J. B., Dattagupta N., Crothers D. M., Biochemistry, 1982, 21, 3933
[24] Satyanarayana S., Dabrowiak J. C., Chaires J. B., Biochemistry, 1993, 32, 2573
[25] Cohen G., Eisenberg H., Biopolymers, 1969, 8, 45
[26] Job P., Ann. Chim., 1928, 9, 113
[27] Mosmann T., J. Immunol. Methods, 1983, 65, 55
[28] Hiort C., Lincoln P., Nordén B., J. Am. Chem. Soc., 1993, 115, 3448
[29] O'Reilly F. M., Kelly J. M., J. Phys. Chem. B, 2000, 104, 7206
[30] Ezadyar S. A., Kumbhar A. S., Kumbhar A. A., Khan A., Polyhedron, 2012, 36, 45
[31] Eriksson M., Mehmedovic M., Westman G., Akerman B., Electrophoresis, 2005, 26, 524
[32] Ju C. C., Zhang A. G., Yuan C. L., Zhao X. L., Wang K. Z., J. Inorg. Biochem., 2011, 105, 435
[33] O'Reilly F. M., Kelly J. M., New. J. Chem., 1998, 22, 215
[34] Onfelt B., Lincoln P., Norden B., J. Am. Chem. Soc., 2001, 123, 3630
[35] Record M. T., Anderson C. F., Lohman T. M., Rev. Biophys., 1978, 11, 103
[36] Tselepi-Kalouli E., Katsaros N., J. Inorg. Biochem.,1989, 37, 271
[37] Neyhart G. A., Grover N., Smith S. R., Kalsbeck W. A., Fairley T. A., Cory M., Thorp H. H., J. Am. Chem. Soc., 1993, 115, 4423
[38] Han M. J., Duan Z. M., Hao Q., Wang K. Z., J. Phys. Chem. C, 2007, 111, 16577
[39] Sigman D. S., Mazumder A., Perrin D. M., Chem. Rev., 1993, 93, 2295
[40] Karna P., Sharp S. M., Yates C., Prakash S., Aneja R., Mol. Cancer, 2009, 8, 93

DNA Binding Properties and Cytotoxic Activities of Two Trinuclear Ruthenium(Ⅱ) Polypyridyl Complexes

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 4

Recommended Articles

Metrics

Comments

[1]	ZHANG Xu, CUI Jiahua, ZHOU Wen, LI Shaoshun. Design, Synthesis and Anticancer Activity of Shikonin and Alkannin Derivatives with Different Substituents on the Naphthazarin Scaffold [J]. Chemical Research in Chinese Universities, 2015, 31(3): 394-400.
[2]	LI Yan-bo, ZHANG Hai-xia, GUO Cai-xia, HU Gui-qin, DU Hai-ying, JIN Ming-hua, HUANG Pei-li, SUN Zhi-wei, YANG Wen-sheng. Cytotoxicity and DNA Damage Effect of TGA-capped CdTe Quantum Dots [J]. Chemical Research in Chinese Universities, 2012, 28(2): 276-281 .
[3]	LIN Xin-li, ZHAO Shu-hua, ZHANG Long, HU Gui-qin, SUN Zhi-wei, YANG Wen-sheng. Dose-dependent Cytotoxicity and Oxidative Stress Induced by “Naked” Fe₃O₄ Nanoparticles in Human Hepatocyte [J]. Chemical Research in Chinese Universities, 2012, 28(1): 114-118.
[4]	ZHANG Jin-chao, SHEN Yong, YANG Meng-su. Synthesis, Characterization and Cytotoxicity of Ammine/Methylamine Platinum(Ⅱ) Complexes with Carboxylates [J]. Chemical Research in Chinese Universities, 2006, 22(3): 278-282.