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Exploring Bioactive Marine Natural Products and Identification of Their Molecular Targets

  • Masayoshi AraiEmail author
Chapter

Abstract

Phenotypic screening is a method that allows detection of compounds that can induce desired phenotypes in cells and microbes. The method shows great potential for discovering compounds with novel mechanisms of action. Discoveries of first-in-class drugs indicate high efficacy of phenotypic screening. Target identification of compounds discovered by phenotypic screening is expected to uncover new metabolic pathways and functions that will lead to the development of novel drug target. Marine organisms like sponges and marine microbes exist in unique habitats and, therefore, produce distinctive secondary metabolites varying from those of terrestrial organisms. They are recently attracting attention as a “seedbed” for novel drug discoveries. We have previously focused on unique phenotypic alterations of cells and pathogenic microbes at the pathologic site of the human body and established phenotypic screening systems searching for bioactive marine natural products, which can regulate such unique phenotypic alterations. Further, implementing the methods of molecular biology and chemical biology, we identified the molecular targets of bioactive marine natural products that we discovered. In this chapter, we introduce our phenotypic screening to explore “medicinal seeds” from marine medicinal resources for novel drug discoveries and also provide identification of molecular targets (binding proteins) of isolated compounds.

Keywords

Marine natural products Molecular target Furospinosulin-1 Dictyoceratin-C Agelasine D 

Notes

Acknowledgments

I would like to express my gratitude to professor emeritus Motomasa Kobayashi and Dr. Naoyuki Kotoku (present affiliation: Colleges of Pharmaceutical Sciences, Ritsumeikan University) for providing their invaluable guidance, comments, suggestions, and cooperation throughout the projects. I am also grateful for the assistance given by all my students and collaborators. These studies were financially supported by Naito Foundation, Hoansha Foundation, Takeda Science Foundation, JST A-STEP (AS242Z00800Q), Osaka University Project MEET, KAKENHI from JSPS or MEXT, and Platform Project for Supporting Drug Discovery and Life Science Research (Basis for Supporting Innovative Drug Discovery and Life Science Research (BINDS)) from AMED under Grant Number JP18am0101084.

References

  1. 1.
    D.C. Swinney, J. Anthony, Nat. Rev. Drug Discov. 10, 507 (2011)Google Scholar
  2. 2.
    S. Omura, T. Fujimoto, K. Otoguro, K. Matsuzaki, R. Moriguchi, H. Tanaka, Y. Sasaki, J. Antibiot. 44, 113 (1991)CrossRefGoogle Scholar
  3. 3.
    S. Omura, K. Matsuzaki, T. Fujmoto, K. Kosuge, T. Furuya, S. Fujita, A. Nakagawa, J. Antibiot. 44, 117 (1991)CrossRefGoogle Scholar
  4. 4.
    G. Fenteany, R.F. Standaert, W.S. Lane, S. Choi, E.J. Corey, S.L. Schreiber, Science 268, 726 (1995)CrossRefGoogle Scholar
  5. 5.
    M.W. Harding, A. Galat, D.E. Uehling, S.L. Schreiber, Nature 341, 758 (1989)CrossRefGoogle Scholar
  6. 6.
    J. Liu, J.D. Farmer Jr., W.S. Lane, J. Friedman, I. Weissman, S.L. Schreiber, Cell 66, 807 (1991)CrossRefGoogle Scholar
  7. 7.
    S. Aoki, Y. Watanabe, M. Sanagawa, A. Setiawan, N. Kotoku, M. Kobayashi, J. Am. Chem. Soc. 128, 3148 (2006)CrossRefGoogle Scholar
  8. 8.
    S. Aoki, Y. Watanabe, D. Tanabe, M. Arai, H. Suna, K. Miyamoto, H. Tsujibo, K. Tsujikawa, H. Yamamoto, M. Kobayashi, Bioorg. Med. Chem. 15, 6758 (2007)CrossRefGoogle Scholar
  9. 9.
    M. Arai, T. Kawachi, A. Setiawan, M. Kobayashi, ChemMedChem 5, 1919 (2010)CrossRefGoogle Scholar
  10. 10.
    M. Arai, T. Kawachi, N. Kotoku, C. Nakata, H. Kamada, S. Tsunoda, Y. Tsutsumi, H. Endo, M. Inoue, H. Sato, M. Kobayashi, ChemBioChem 17, 181 (2016)CrossRefGoogle Scholar
  11. 11.
    M. Arai, T. Kawachi, H. Sato, A. Setiawan, M. Kobayashi, Bioorg. Med. Chem. Lett. 24, 3155 (2014)CrossRefGoogle Scholar
  12. 12.
    Y. Sumii, N. Kotoku, A. Fukuda, T. Kawachi, Y. Sumii, M. Arai, M. Kobayashi, Bioorg. Med. Chem. 23, 966 (2015)CrossRefGoogle Scholar
  13. 13.
    Y. Sumii, N. Kotoku, A. Fukuda, T. Kawachi, M. Arai, M. Kobayashi, Mar. Drugs 13, 7419 (2015)CrossRefGoogle Scholar
  14. 14.
    N. Kotoku, R. Ishida, H. Matsumoto, M. Arai, K. Toda, A. Setiawan, O. Muraoka, M. Kobayashi, J. Org. Chem. 82, 1705 (2017)CrossRefGoogle Scholar
  15. 15.
    M. Arai, H. Niikawa, M. Kobayashi, J. Nat. Med. 67, 271 (2013)CrossRefGoogle Scholar
  16. 16.
    S. Ishida, M. Arai, H. Nikawa, M. Kobayashi, Biol. Pharm. Bull. 34, 917 (2011)CrossRefGoogle Scholar
  17. 17.
    M. Arai, M. Sobou, C. Vilchèze, A. Baughn, H. Hashizume, P. Pruksakorn, S. Ishida, M. Matsumoto, W.R. Jacobs Jr., M. Kobayashi, Bioorg. Med. Chem. 16, 6732 (2008)CrossRefGoogle Scholar
  18. 18.
    M. Arai, S. Ishida, A. Setiawan, M. Kobayashi, Chem. Pharm. Bull. 57, 1136 (2009)CrossRefGoogle Scholar
  19. 19.
    M. Arai, L. Liu, T. Fujimoto, A. Setiawan, M. Kobayashi, Mar. Drugs 9, 984 (2011)CrossRefGoogle Scholar
  20. 20.
    M. Arai, Y. Yamano, A. Setiawan, M. Kobayashi, ChemBioChem 15, 117 (2014)CrossRefGoogle Scholar
  21. 21.
    M. Arai, Y. Yamano, K. Kamiya, A. Setiawan, M. Kobayashi, J. Nat. Med. 70, 467 (2016)CrossRefGoogle Scholar
  22. 22.
    M. Arai, K. Kamiya, P. Pruksakorn, Y. Sumii, N. Kotoku, J.P. Joubert, P. Moodley, C. Han, S. Dayoung, M. Kobayashi, Bioorg. Med. Chem. 23, 3534 (2015)CrossRefGoogle Scholar
  23. 23.
    P. Pruksakorn, M. Arai, N. Kotoku, C. Vilchèze, A.D. Baughn, P. Moodley, W.R. Jacobs Jr., M. Kobayashi, Bioorg. Med. Chem. Lett. 20, 3658 (2010)CrossRefGoogle Scholar
  24. 24.
    M.H. Larsen, C. Vilchèze, L. Kremer, G.S. Besra, L. Parsons, M. Salfinger, L. Heifets, M.H. Hazbon, D. Alland, J.C. Sacchettini, W.R. Jacobs Jr., Mol. Microbiol. 46, 453 (2002)CrossRefGoogle Scholar
  25. 25.
    P. Pruksakorn, M. Arai, L. Liu, P. Moodley, W.R. Jacobs Jr., M. Kobayashi, Biol. Pharm. Bull. 34, 1287 (2011)CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Graduate School of Pharmaceutical SciencesOsaka UniversitySuitaJapan

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