Structure-related cytotoxic activity of derivatives from kulokekahilide-2, a cyclodepsipeptide in Hawaiian marine mollusk

Masahiro Umehara, Takayuki Negishi, Tomoko Tashiro, Youichi Nakao, Junji Kimura

    Research output: Contribution to journal › Article

    10 Citations (Scopus)

    Abstract

    Kulokekahilide-2, a 26-membered cyclodepsipeptide, was isolated from Hawaiian marine mollusk and possessed potent cytotoxicity in mammalian tumor cells. In the present study, we synthesized kulokekahilide-2 and its derivatives and examined the structure-activity relationships of these peptides in human cancer cells (A549, K562, and MCF7 cells). This study demonstrated that the cyclization of depsipeptide and the chirality of the 21 position in Ala in kulokekahilide-2 were important for its cytotoxic property and that addition of halogen at the para position of phenyl group in the 24-d-MePhe in kulokekahilide-2 as well as some derivatives remarkably increased their cytotoxicity in human cancer cells. These results suggest that the modifications of 24-d-MePhe in kulokekahilide-2, preserving its cyclization and the chirality at the 21-position, are promising strategy for exploring new derivative of kulokekahilide-2 as anti-tumor drug.

    Original languageEnglish
    Pages (from-to)7422-7425
    Number of pages4
    JournalBioorganic and Medicinal Chemistry Letters
    Volume22
    Issue number24
    DOIs
    Publication statusPublished - 2012 Dec 15

    Fingerprint

    Depsipeptides
    Mollusca
    Derivatives
    Chirality
    Cyclization
    Cells
    Cytotoxicity
    Tumors
    Neoplasms
    Halogens
    K562 Cells
    MCF-7 Cells
    Structure-Activity Relationship
    kulokekahilide-2
    Peptides
    Pharmaceutical Preparations

    Keywords

    • Cyclodepsipeptide
    • Cytotoxic activity
    • Kulokekahilide-2
    • Structure-activity relationship

    ASJC Scopus subject areas

    • Pharmaceutical Science
    • Drug Discovery
    • Organic Chemistry
    • Molecular Medicine
    • Molecular Biology
    • Clinical Biochemistry
    • Biochemistry

    Cite this

    Structure-related cytotoxic activity of derivatives from kulokekahilide-2, a cyclodepsipeptide in Hawaiian marine mollusk. / Umehara, Masahiro; Negishi, Takayuki; Tashiro, Tomoko; Nakao, Youichi; Kimura, Junji.

    In: Bioorganic and Medicinal Chemistry Letters, Vol. 22, No. 24, 15.12.2012, p. 7422-7425.

    Research output: Contribution to journal › Article

    Umehara, M, Negishi, T, Tashiro, T, Nakao, Y & Kimura, J 2012, 'Structure-related cytotoxic activity of derivatives from kulokekahilide-2, a cyclodepsipeptide in Hawaiian marine mollusk', Bioorganic and Medicinal Chemistry Letters, vol. 22, no. 24, pp. 7422-7425. https://doi.org/10.1016/j.bmcl.2012.10.058
    Umehara M, Negishi T, Tashiro T, Nakao Y, Kimura J. Structure-related cytotoxic activity of derivatives from kulokekahilide-2, a cyclodepsipeptide in Hawaiian marine mollusk. Bioorganic and Medicinal Chemistry Letters. 2012 Dec 15;22(24):7422-7425. https://doi.org/10.1016/j.bmcl.2012.10.058
    Umehara, Masahiro ; Negishi, Takayuki ; Tashiro, Tomoko ; Nakao, Youichi ; Kimura, Junji. / Structure-related cytotoxic activity of derivatives from kulokekahilide-2, a cyclodepsipeptide in Hawaiian marine mollusk. In: Bioorganic and Medicinal Chemistry Letters. 2012 ; Vol. 22, No. 24. pp. 7422-7425.
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