Synthesis and Biological Evaluation of the 12,12-Dimethyl Derivative of Aplog-1, an Anti-Proliferative Analog of Tumor-Promoting Aplysiatoxin

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Author(s)

Abstract

Aplog-1 is a unique analog of tumor-promoting aplysiatoxin that inhibits tumor-promotion by phorbol diesters and proliferation of tumor cells. While the structural features relevant to the biological activities of Aplog-1 remain to be identified, recent studies by us have suggested that local hydrophobicity around the spiroketal moiety of Aplog-1 is a crucial determinant of its anti-proliferative activity. This hypothesis led us to design 12,12-dimethyl-Aplog-1 (<B>3</B>), in which a hydrophobic geminal dimethyl group is installed proximal to the spiroketal moiety to improve biological potency. As expected, <B>3</B> was more effective than Aplog-1 in inhibiting cancer cell growth and binding to protein kinase Cδ, a putative receptor responsible for the biological response of Aplog-1. Moreover, an induction test on Epstein-Barr virus early antigen demonstrated <B>3</B> to be a better anti-tumor promoter than Aplog-1. These results indicate that <B>3</B> is a superior derivative of Aplog-1, and thus a more promising lead for anti-cancer drugs.

Journal

  • Bioscience, Biotechnology, and Biochemistry

    Bioscience, Biotechnology, and Biochemistry 75(6), 1167-1173, 2011-06-23

    Japan Society for Bioscience, Biotechnology, and Agrochemistry

References:  32

Codes

  • NII Article ID (NAID)
    10029328423
  • NII NACSIS-CAT ID (NCID)
    AA10824164
  • Text Lang
    ENG
  • Article Type
    ART
  • ISSN
    09168451
  • NDL Article ID
    11132014
  • NDL Source Classification
    ZR7(科学技術--農林水産--農産) // ZR2(科学技術--生物学--生化学) // ZP1(科学技術--化学・化学工業)
  • NDL Call No.
    Z53-G223
  • Data Source
    CJP  NDL  IR  J-STAGE 
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