Bisintercalator natural products with potential therapeutic applications: isolation, structure determination, synthetic and biological studies

Simon Dawson, John P. Malkinson, David Paumier, Mark Searcey

    Research output: Contribution to journalArticlepeer-review

    86 Citations (Scopus)

    Abstract

    Echinomycin is the prototypical bisintercalator, a molecule that binds to DNA by inserting two planar chromophores between the base-pairs of duplex DNA, placing its cyclic depsipeptide backbone in the minor groove. As such, it has been the focus of an extensive number of investigations into its biological activity, nucleic acid binding and, to some extent, its structure - activity relationships. However, echinomycin is also the parent member of an extended family of natural products that interact with DNA by a similar mechanism of bisintercalation. The structural variety in these compounds leads to changes in sequence selectivity and biological activity, particularly as anti-tumour and anti-viral agents. One of the more recently identified marine natural products that is moving close to clinical development is thiocoraline, and it therefore seems timely to review the various bisintercalator natural products.
    Original languageEnglish
    Pages (from-to)109-126
    Number of pages18
    JournalNatural Product Reports
    Volume24
    Issue number1
    DOIs
    Publication statusPublished - 2007

    Keywords

    • SEQUENCE-SPECIFIC BINDING
    • PHASE-II TRIAL
    • ACID
    • KEY SANDRAMYCIN ANALOGS
    • COMPLEX
    • CONSTITUENT AMINO
    • MODIFIED DNA-MOLECULES
    • GYNECOLOGIC-ONCOLOGY-GROUP
    • STOFFWECHSELPRODUKTE VON ACTINOMYCETEN
    • QUINOXAPEPTIN A-C
    • TUMOR ANTIBIOTIC
    • DES-N-TETRAMETHYLTRIOSTIN

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