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Synthesis and biological evaluation of new mono naphthalimide platinum(IV) derivatives as antitumor agents with dual DNA damage mechanism

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Abstract

Naphthalimide has emerged as an interesting DNA intercalator and possessed attracting antitumor properties. In this context, naphthalimide group was linked to platinum(IV) core to construct a series of new mono naphthalimide platinum(IV) derivatives. The title compounds exert effective antitumor activities to the tested tumor cells lines in vitro, especially the one with propionyl chain displays comparable or even better bioactivities than platinum(II) reference drugs cisplatin and oxaliplatin. Moreover, the mono naphthalimide platinum(IV) derivative displays comparable tumor growth inhibitory competence against CT26 xenograft tumors in BALB/c mice in vivo without severe toxic effects in contrast to oxaliplatin. A dual DNA damage mechanism was proven for the title complex. Both naphthalimide ligand and the liberated platinum(II) moiety could generate DNA lesions to tumor cells synergistically and active the apoptotic pathway by up-regulating the expression of caspase 9 and caspase 3. Meanwhile, the conversion of platinum(II) drug into tetravalent form by incorporating naphthalimide moiety increases the uptake of platinum in whole cells and DNA remarkably. All these facts might be the factors for the title platinum(IV) complexes to overcome platinum(II) drug resistance. Additionally, the mono naphthalimide platinum(IV) complex could interact with human serum albumin by hydrogen bond and van der Waals force which would further influence their storage, transport and bioactivities.

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References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) CA Cancer J Clin 68:394

    Article  Google Scholar 

  2. Allemani C, Matsuda T, Carlo DV, Harewood R, Matz M, Nikšić M, Bonaventure A, Valkov M, Johnson CJ, Estève J, Ogunbiyi OJ, Silva GA, Chen WQ, Eser S, Engholm G, Stiller CA, Monnereau A, Woods RR, Visser O, Lim GH, Aitken J, Weir HK, Coleman MP (2018) Lancet 391:1023

    Article  Google Scholar 

  3. Wong E, Christen MG (1999) Chem Rev 99:2451

    Article  CAS  Google Scholar 

  4. Allardyce CS, Dyson PJ (2016) Dalton Trans 45:3201

    Article  CAS  Google Scholar 

  5. Wheate NJ, Walker S, Craig GE, Oun R (2010) Dalton Trans 39:8113

    Article  CAS  Google Scholar 

  6. Oun R, Mouss YE, Wheate NJ (2018) Dalton Trans 47:6645

    Article  CAS  Google Scholar 

  7. Johnstone TC, Suntharalingam K, Lippard SJ (2016) Chem Rev 116:3436

    Article  CAS  Google Scholar 

  8. Gibson D (2016) Dalton Trans 45:12983

    Article  CAS  Google Scholar 

  9. Schreiber-Brynzak E, Pichler V, Heffeter P, Hanson B, Theiner S, Lichtscheidl-Schultz I, Kornauth C, Bamonti L, Dhery V, Groza D, Berry D, Berger W, Galanski M, Jakupec MA, Keppler BK (2016) Metallomics 8:422

    Article  CAS  Google Scholar 

  10. Tan XX, Li GS, Wang QP, Wang BQ, Li DC, Wang PG (2018) Prog Chem 30:831

    Google Scholar 

  11. Wexselblatt E, Gibson D (2012) J Inorg Biochem 117:220

    Article  CAS  Google Scholar 

  12. Basu U, Banik B, Wen R, Pathak RK, Dhar S (2016) Dalton Trans 45:12992

    Article  CAS  Google Scholar 

  13. Gabano E, Ravera M, Osella D (2014) Dalton Trans 43:9813

    Article  CAS  Google Scholar 

  14. Liu H, Ma J, Li Y, Yue K, Li L, Xi Z, Zhang X, Liu J, Feng K, Ma Q, Liu S, Guo S, Wang PG, Wang C, Xie S (2019) J Med Chem 62:11324

    Article  CAS  Google Scholar 

  15. Ma J, Liu H, Xi Z, Hou J, Li Y, Niu J, Liu T, Bi S, Wang X, Wang C, Wang J, Xie S, Wang PG (2018) Front Chem 6:386

    Article  CAS  Google Scholar 

  16. Chen Z, Liang X, Zhang HY, Xie H, Liu JW, Xu YF, Zhu WP, Wang Y, Wang X, Tan SY, Kuang D, Qian XH (2010) J Med Chem 53:2589

    Article  CAS  Google Scholar 

  17. Seliga R, Pilatova M, Sarissky M, Viglasky V, Walko M, Mojzis J (2013) Mol Biol Rep 40:4129

    Article  CAS  Google Scholar 

  18. El-Azab AS, Alanazi AM, Abdel-Aziz NI, Al-Suwaidan IA, El-Sayed MAA, El-Sherbeny MA, Abdel-Aziz AAM (2013) Med Chem Res 22:2360

    Article  CAS  Google Scholar 

  19. Chua EY, Davey GE, Chin CF, Dröge P, Ang WH, Davey CA (2015) Nucleic Acids Res 43:5285

    Article  Google Scholar 

  20. Pérez JM, López-Solera I, Montero EI, Braña MF, Alonso C, Robinson SP, Navarro-Ranninger C (1999) J Med Chem 42:5482

    Article  Google Scholar 

  21. Herrera JM, Mendes F, Gama S, Santos I, Navarro-Ranninger C, Cabrera S, Quiroga AG (2014) Inorg Chem 53:12627

    Article  CAS  Google Scholar 

  22. Navas F, Mendes F, Santos I, Navarro RC, Cabrera S, Quiroga AG (2017) Inorg Chem 56:6175

    Article  CAS  Google Scholar 

  23. Wang QP, Li GS, Liu ZF, Tan XX, Ding Z, Ma J, Li LJ, Li DC, Han J, Wang BQ (2018) Eur J Inorg Chem 40:4442

    Article  Google Scholar 

  24. Wang QP, Tan XX, Liu ZF, Li GS, Zhang RY, Wei JJ, Wang SB, Li DC, Wang BQ, Han J (2018) Eur J Pharm Sci 124:127

    Article  CAS  Google Scholar 

  25. Li GS, Zhang JF, Liu ZF, Wang QP, Chen Y, Liu M, Li DC, Han J, Wang BQ (2019) J Inorg Biochem 194:34

    Article  CAS  Google Scholar 

  26. Wang QP, Chen Y, Li GS, Liu ZF, Ma J, Liu M, Li DC, Han J, Wang BQ (2019) Bioorg Med Chem 27:2112

    Article  CAS  Google Scholar 

  27. Wang Q, Huang Z, Ma J, Lu X, Zhang L, Wang X, Wang PG (2016) Dalton Trans 45:10366

    Article  CAS  Google Scholar 

  28. Ma J, Wang Q, Huang Z, Yang X, Nie Q, Hao W, Wang PG, Wang X (2017) J Med Chem 60:5736

    Article  CAS  Google Scholar 

  29. Wang Q, Chen Y, Li G, Zhao Y, Liu Z, Zhang R, Liu M, Li D, Han J (2019) Bioorg Med Chem Lett 29:126670

    Article  CAS  Google Scholar 

  30. Quaquebeke EV, Mahieu T, Dumont P, Dewelle J, Ribaucour F, Simon G, Sauvage S, Gaussin JF, Tuti J, Yazidi ME, Vynckt FV, Mijatovic T, Lefranc F, Darro F, Kiss R (2007) J Med Chem 50:4122

    Article  Google Scholar 

  31. Göschl S, Schreiber-Brynzak E, Pichler V, Cseh K, Heffeter P, Jungwirth U, Jakupec MA, Bergerbcd W, Keppler BK (2017) Metallomics 9:309

    Article  Google Scholar 

  32. Jungwirth U, Xanthos DN, Gojo J, Bytzek AK, Körner W, Heffeter P, Abramkin SA, Jakupec MA, Hartinger CG, Windberger U, Galanski M, Keppler BK, Berger W (2012) Mol Pharmacol 81:719

    Article  CAS  Google Scholar 

  33. Wei Q, Dong JF, Zhao PR, Li MM, Cheng FL, Kong JM, Li LZ (2016) J Photochem Photobiol B 161:355

    Article  CAS  Google Scholar 

  34. Zhao PR, Wei Q, Dong JF, Ding FF, Li JH, Li LZ (2016) J Coord Chem 69:2437

    Article  CAS  Google Scholar 

  35. Li XL, Hu YJ, Wang H, Yu BQ, Yue HL (2012) Biomacromolecules 13:873

    Article  CAS  Google Scholar 

  36. Yuan LX, Liu M, Liu GQ, Li DC, Wang ZP, Wang BQ, Han J, Zhang M (2017) Spectrochim Acta A 173:584

    Article  CAS  Google Scholar 

  37. Yuan LX, Liu M, Sun B, Liu J, Wei XL, Wang ZP, Wang BQ, Han J (2017) J Mol Liq 248:330

    Article  CAS  Google Scholar 

  38. Mayr J, Heffeter P, Groza D, Galvez L, Koellensperger G, Roller A, Alte B, Haider M, Berger W, Kowol CR, Keppler BK (2017) Chem Sci 8:2241

    Article  CAS  Google Scholar 

  39. Yuan LX, Liu M, Shi YB, Yan H, Han J, Liu LY (2018) J Biomol Struct Dyn 37:2776

    Article  Google Scholar 

Download references

Acknowledgements

The work was supported by National Natural Science Foundation of China (No. 21807056), Natural Science Foundation of Shandong (No. ZR2017BH092), Doctoral Foundation of Liaocheng University (No. 318051635), Open Project of Shandong Collaborative Innovation Center for Antibody Drugs (No. CIC-AD1836, CIC-AD1835), National Science and Technology Major Project of China (No. 2017ZX09201-003) and Taishan Scholar Research Foundation. This work was also technically supported by Shandong Collaborative Innovation Center for Antibody Drugs and Engineering Research Center for Nanomedicine and Drug Delivery Systems.

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Authors and Affiliations

  1. Institute of Biopharmaceutical Research, Liaocheng University, Liaocheng, 252059, People’s Republic of China

    Zuojie Li, Yan Chen, Zhifang Liu, Qingpeng Wang, Yanna Zhao, Min Liu, Zhengping Wang, Dacheng Li & Jun Han

  2. College of Chemistry, Chemical Engineering and Materials Science, Shandong Normal University, Jinan, 250014, People’s Republic of China

    Jinjian Wei

  3. Shandong Provincial Key Laboratory of Chemical Energy Storage and Novel Cell Technology, Liaocheng University, Liaocheng, 252059, People’s Republic of China

    Dacheng Li

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  1. Zuojie Li
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  2. Yan Chen
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  7. Min Liu
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Correspondence to Qingpeng Wang, Min Liu or Dacheng Li.

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Li, Z., Chen, Y., Liu, Z. et al. Synthesis and biological evaluation of new mono naphthalimide platinum(IV) derivatives as antitumor agents with dual DNA damage mechanism. Monatsh Chem 151, 353–367 (2020). https://doi.org/10.1007/s00706-020-02561-1

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  • DOI: https://doi.org/10.1007/s00706-020-02561-1

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