Ruthenium(II) polypyridyl complexes: synthesis, cytotoxicity in vitro, reactive oxygen species, mitochondrial membrane potential and cell cycle arrest studies

详细信息    查看全文

• 作者：Bing-Jie Han ; Guang-Bin Jiang ; Ji Wang ; Wei Li…
• 刊名：Transition Metal Chemistry
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：40
• 期：2
• 页码：153-160
• 全文大小：3,698 KB
• 参考文献：1. Lippert B (1999) Cisplatin, chemistry and biochemistry of a leading anticancer drug. Wiley-VCH, Weinheim CrossRef
  2. Gill MR, Thomas JA (2012) Chem Soc Rev 4:3179-192 CrossRef
  3. Neidle S (2002) Nucleic acid structure and recognition. Oxford University Press, Oxford
  4. Bruijnincx PC, Sadler PJ (2008) Curr Opin Chem Biol 12:197-06 CrossRef
  5. Han BJ, Jiang GB, Wang J, Li W, Huang HL, Liu YJ (2014) RSC Adv 4:40899-0906 CrossRef
  6. Tan CP, Lai SS, Wu SH, Hu S, Zhou LJ, Chen Y, Wang MX, Zhu YP, Lian W, Peng WL, Ji LN, Xu AL (2010) J Med Chem 53:7613-624 CrossRef
  7. Jiang GB, Li W, Wang J, Han BJ, Lin GJ, Xie YY, Huang HL, Liu YJ (2014) Transit Met Chem 39:849-58 CrossRef
  8. Hartinger CG, Selfried SZ, Jakupee MA, Kynast B, Zorbas H, Keppler BK (2006) J Inorg Biochem 100:891-04 CrossRef
  9. Xie YY, Huang HL, Yao JH, Lin GJ, Jiang GB, Liu YJ (2013) Eur J Med Chem 63:603-10 CrossRef
  10. Yaw KY, Michael M, Abraha H, Peter JS (2005) Chem Commun 38:4764-776
  11. Jiang GB, Zheng X, Yao JH, Han BJ, Li W, Wang J, Huang HL, Liu YJ (2014) J Inorg Biochem 141:170-79 CrossRef
  12. Alessio E, Mestroni G, Bergamo A, Sava G (2004) Curr Top Med Chem 4:1525-535 CrossRef
  13. Jiang GB, Xie YY, Lin GJ, Huang HL, Liang ZH, Liu YJ (2013) J Photochem Photobiol B Biol 129:48-6 CrossRef
  14. Devi CS, Nagababu P, Reddy VV, Sateesh V, Srishailam A, Satyanarayana S (2014) Aust J Chem 67:225-33
  15. Li W, Jiang GB, Yao JH, Wang XZ, Wang J, Han BJ, Xie YY, Lin GJ, Huang HL, Li YJ (2014) J Photochem Photobiol B Biol 140:94-04 CrossRef
  16. Bergamo A, Sava G (2007) Dalton Trans 13:1267-272 CrossRef
  17. Hartinger CG, Jakupec MA, Zorbas SS, Groessl M, Egger A, Berger W, Zorbas H, Dyson PJ, Keppler BK (2008) Chem Biodivers 5:2140-155 CrossRef
  18. Hotze ACG, Bacac M, Velders AH, Jansen BAJ, Kooijman H, Spek AL, Haasnoot JG, Reedijk J (2003) J Med Chem 46:1743-750 CrossRef
  19. Schatzschneider U, Niesel J, Ott I, Gust R, Alborzinia H, Wolfl S (2008) Chem Med Chem 3:1104-109 CrossRef
  20. Lin GJ, Jiang GB, Xie YY, Huang HL, Liang ZH, Liu YJ (2013) J Biol Inorg Chem 18:873-82 CrossRef
  21. Devi CS, Nagababu P, Natarajan S, Deepika N, Reddy PV, Veerababu N, Singh SS, Satyanarayana S (2014) Eur J Med Chem 72:160-69 CrossRef
  22. Zhang JN, Yu QQ, Li Q, Yang LC, Chen LM, Zhou YH, Liu YA (2014) J Inorg Biochem 134:1-1 CrossRef
  23. Liu XW, Xu LC, Li H, Chao H, Zheng KC, Ji LN (2009) J Mol Struct 920:163-71 ruc.2008.10.038" target="_blank" title="It opens in new window">CrossRef
  24. Sullivan BP, Salmon DJ, M
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Catalysis
  Physical Chemistry
  Inorganic Chemistry
  
• 出版者：Springer Netherlands
• ISSN：1572-901X

文摘

Two Ru(II) polypyridyl complexes [Ru(dmb)2(idpq)](ClO4)2 (1) (idpq?=?indeno[1,2-b]dipyrido[3,2-f:2-3-h]-quinoxaline-6-one, dmb?=?4,4-dimethyl-2,2-bipyridine) and [Ru(bpy)2(idpq)](ClO4)2 (2) (bpy?=?2,2-bipyridine) have been synthesized and characterized. Their in vitro cytotoxicities, apoptosis, cellular uptake, production of reactive oxygen species (ROS), mitochondrial membrane potential assays and effects on cell cycle distribution were studied. The IC50 values range from 13.1?±?1.1 to 30.9?±?3.1?μM. Complex 1 is toxic to HeLa cells with an IC50 value of 13.1?±?1.1?μM, while complex 2 shows relatively high cytotoxicity against HepG-2 cells. However, both complexes exhibit lower cytotoxicity than cisplatin toward selected cell lines under identical conditions. Both complexes can induce apoptosis and cell cycle arrest at the S and G0/G1 phases in HeLa cells, respectively. In addition, both Ru(II) complexes, which can be effectively taken up by HeLa cells, induced generation of intracellular ROS in a concentration-dependent manner and produced a decrease in mitochondrial membrane potential. The results show that these complexes induce apoptosis in HeLa cells through a ROS-mediated mitochondrial dysfunction pathway.