Semisynthesis, biological activity, and molecular modeling studies of C-ring-modified camptothecins

Cristian Samorì, Andrea Guerrini, Greta Varchi, Gabriele Fontana, Ezio Bombardelli, Stella Tinelli, Giovanni Luca Beretta, Serena Basili, Stefano Moro, Franco Zunino, Arturo Battaglia

    Research output: Contribution to journalArticlepeer-review

    32 Scopus citations

    Abstract

    The synthesis, biological activity, and molecular modeling studies of C-ring-modified camptothecins are reported. A general synthetic protocol, based on "C-5 camptothecin (C-5-CPT) enolate chemistry", allows one to obtain various C5-substituted analogues. All new compounds, obtained as 1:1 epimeric mixtures, were tested for their antiproliferative activity. Experimental data showed that all novel derivatives are less active than the reference compounds and that one of the two epimers is more active than the other. Molecular docking simulations were performed to achieve more insight into the interactions between the new C5- modified CPTs and Topo I. A good correlation was observed when the data of cytotoxicity and the values calculated for the free binding energy were combined.

    Original languageEnglish (US)
    Pages (from-to)1029-1039
    Number of pages11
    JournalJournal of Medicinal Chemistry
    Volume52
    Issue number4
    DOIs
    StatePublished - Feb 26 2009

    ASJC Scopus subject areas

    • Molecular Medicine
    • Drug Discovery

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