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Fullerene Derivatives as Antiviral and Anticancer Agents

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Handbook of Fullerene Science and Technology

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Abstract

Fullerenes represent a new molecular form of carbon that is of interest for the unique chemical and physical properties and may be novel lead compounds for drug discovery. However, one of the major issues that prevents the application of fullerenes in the biomedical field is their poor solubility in water, which is related to their high hydrophobic character. To overcome this issue, hydrophilic groups have been incorporated into the fullerene core. These fullerene derivatives possess inhibitory activities against human immunodeficiency virus (HIV) protease, HIV reverse transcriptase protease, HCV NS5B RNA polymerase, and hepatitis C virus (HCV) NS3/4A protease. Therefore, fullerene derivatives may be used as antiviral agents. In addition, some kinds of fullerene derivatives exhibit antiproliferative activities by inducing apoptosis resulting from the generation of reactive oxygen species. In this way, fullerene derivatives have the potential to be new anticancer agents.

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References

  1. Kroto HW, Heath JR, OʼBrien SC et al (1985) C60: Buckminsterfullerene. Nature 318:162–163

    Article  CAS  Google Scholar 

  2. Bingel C (1993) Cyclopropanierung von Fullerenen. Chem Ber 126:1957–1959

    Article  CAS  Google Scholar 

  3. Prato M (1997) [60] Fullerene chemistry for materials science applications. J Mater Chem 7:1097–1109

    Article  CAS  Google Scholar 

  4. Barre-Sinoussi F, Chermann JC, Rey F et al (1983) Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220:868–871

    Article  CAS  Google Scholar 

  5. Bartlett JA, Fath MJ, Demasi R et al (2006) An updated systematic overview of triple combination therapy in antiretroviral-naive HIV-infected adults. AIDS 20:2051–2064

    Article  CAS  Google Scholar 

  6. Friedman SH, DeCamp DL, Sijbesma RP et al (1993) Inhibition of the HIV-1 protease by fullerene derivatives: model building studies and experimental verification. J Am Chem Soc 115:6506–6509

    Article  CAS  Google Scholar 

  7. Friedman SH, Ganapathi PS, Rubin Y et al (1998) Optimizing the binding of fullerene inhibitors of the HIV-1 protease through predicted increases in hydrophobic desolvation. J Med Chem 41:2424–2429

    Article  CAS  Google Scholar 

  8. Cohen KA, Hopkins J, Ingraham RH et al (1991) Characterization of the binding site for nevirapine (BI-RG-587), a nonnucleoside inhibitor of human immunodeficiency virus type-1 reverse transcriptase. J Biol Chem 266:14670–14674

    Article  CAS  Google Scholar 

  9. Smerdon SJ, Jäger J, Wang J et al (1995) Structure of the binding site for nonnucleoside inhibitors of the reverse transcriptase of human immunodeficiency virus type 1. Proc Natl Acad Sci USA 91:3911–3915

    Article  Google Scholar 

  10. Mashino T, Shimotohno K, Ikegami N et al (2005) Human immunodeficiency virus-reverse transcriptase inhibition and hepatitis C virus RNA-dependent RNA polymerase inhibition activities of fullerene derivatives. Bioorg Med Chem Lett 15:1107–1109

    Article  CAS  Google Scholar 

  11. Nakamura S, Ikegami N, Harada M et al (2006) Synthesis of novel amino acid-type fullerenes and their inhibition activity of HIV reverse transcriptase and HCV RNA polymerase. J Kyoritsu Univ Pharm 1:77–84

    CAS  Google Scholar 

  12. Nakamura S, Mashino T (2009) Biological activities of water-soluble fullerene derivatives. J Phys Conf Ser 159:012003

    Article  Google Scholar 

  13. Yasuno T, Ohe T, Takahashi K et al (2015) The human immunodeficiency virus-reverse transcriptase inhibition activity of novel pyridine/pyridinium-type fullerene derivatives. Bioorg Med Chem Lett 25:3226–3229

    Article  CAS  Google Scholar 

  14. Yang NJ, Hinner MJ (2015) Getting across the cell membrane: an overview for small molecules, peptides, and proteins. Methods Mol Biol 1266:29–53

    Article  CAS  Google Scholar 

  15. Kelly TA, Proudfoot JR, McNeil DW et al (1995) Novel non-nucleoside inhibitors of human immunodeficiency virus type 1 reverse transcriptase. 5. 4-Substituted and 2,4-disubstituted analogs of nevirapine. J Med Chem 38:4839–4847

    Article  CAS  Google Scholar 

  16. Das K, Clark AD Jr, Lewi PJ et al (2004) Roles of conformational and positional adaptability in structure-based design of TMC125-R165335 (etravirine) and related non-nucleoside reverse transcriptase inhibitors that are highly potent and effective against wild-type and drug-resistant HIV-1 variants. J Med Chem 47:2550–2560

    Article  CAS  Google Scholar 

  17. Choo QL, Kuo G, Weiner AJ et al (1989) Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science 244:359–362

    Article  CAS  Google Scholar 

  18. Götte M, Feld JJ (2016) Direct-acting antiviral agents for hepatitis C: structural and mechanistic insights. Nat Rev Gastroenterol Hepatol 13:338–351

    Article  Google Scholar 

  19. Kataoka H, Ohe T, Takahashi K et al (2016) Novel fullerene derivatives as dual inhibitors of Hepatitis C virus NS5B polymerase and NS3/4A protease. Bioorg Med Chem Lett 26:4565–4567

    Article  CAS  Google Scholar 

  20. Gibbs JB (2000) Mechanism-based target identification and drug discovery in cancer research. Science 287:1969–1973

    Article  CAS  Google Scholar 

  21. Goldman B (2003) Multidrug resistance: can new drugs help chemotherapy score against cancer? J Natl Cancer Inst 95:255–257

    Article  Google Scholar 

  22. Liu Y, Chen C, Qian P et al (2015) Gd-metallofullerenol nanomaterial as non-toxic breast cancer stem cell-specific inhibitor. Nat Commun 6:5988

    Article  CAS  Google Scholar 

  23. Kang SG, Zhou G, Yang P et al (2012) Molecular mechanism of pancreatic tumor metastasis inhibition by Gd@C82(OH)22 and its implication for de novo design of nanomedicine. Proc Natl Acad Sci USA 109:15431–15436

    Article  CAS  Google Scholar 

  24. Chen C, **ng G, Wang J et al (2005) Multihydroxylated [Gd@C82(OH)22]n nanoparticles: antineoplastic activity of high efficiency and low toxicity. Nano Lett 5:2050–2057

    Article  CAS  Google Scholar 

  25. Mashino T, Nishikawa D, Takahashi K et al (2003) Antibacterial and antiproliferative activity of cationic fullerene derivatives. Bioorg Med Chem Lett 13:4395–4397

    Article  CAS  Google Scholar 

  26. Funakoshi-Tago M, Nagata T, Tago K et al (2012) Fullerene derivative prevents cellular transformation induced by JAK2 V617F mutant through inhibiting c-Jun N-terminal kinase pathway. Cell Signal 24:2024–2034

    Article  CAS  Google Scholar 

  27. Funakoshi-Tago M, Tsukada M, Watanabe T et al (2014) Effect of chemical modification on the ability of pyrrolidinium fullerene to induce apoptosis of cells transformed by JAK2 V617F mutant. Int Immunopharmacol 20:258–263

    Article  CAS  Google Scholar 

  28. Nishizawa C, Hashimoto N, Yokoo S et al (2009) Pyrrolidinium-type fullerene derivative-induced apoptosis by the generation of reactive oxygen species in HL-60 cells. Free Radical Res 43:1240–1247

    Article  CAS  Google Scholar 

  29. Yasuno T, Ohe T, Ikeda H et al (2019) Synthesis and antitumor activity of novel pyridinium fullerene derivatives. Int J Nanomedicine 14:6325–6337

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Faculty of Pharmacy, Keio University, Tokyo, Japan

    Tomoyuki Ohe & Tadahiko Mashino

Authors
  1. Tomoyuki Ohe
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  2. Tadahiko Mashino
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Corresponding author

Correspondence to Tomoyuki Ohe .

Editor information

Editors and Affiliations

  1. School of Materials Science and Eng., Huazhong University of Science and Technology., Wuhan, Hubei, China

    **ng Lu

  2. Foundation for Advancement of International Science, Tsukuba, Japan

    Takeshi Akasaka

  3. School of Materials Science and Engineering, Huangzhou University of Science and Technology, Wuhan, Hebei, China

    Zdenek Slanina

Section Editor information

  1. State Key Laboratory of Materials Processing and Die & Mould Technology, Huazhong University of Science and Technology , School of Materials Science and Engineering, Wuhan, China

    **ng Lu

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© 2021 Springer Nature Singapore Pte Ltd.

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Ohe, T., Mashino, T. (2021). Fullerene Derivatives as Antiviral and Anticancer Agents. In: Lu, X., Akasaka, T., Slanina, Z. (eds) Handbook of Fullerene Science and Technology. Springer, Singapore. https://doi.org/10.1007/978-981-13-3242-5_38-1

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  • DOI: https://doi.org/10.1007/978-981-13-3242-5_38-1

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  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-3242-5

  • Online ISBN: 978-981-13-3242-5

  • eBook Packages: Springer Reference Chemistry and Mat. ScienceReference Module Physical and Materials ScienceReference Module Chemistry, Materials and Physics

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