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  • Title: Synthesis and cytotoxic evaluation of novel spirohydantoin derivatives of the dihydrothieno[2,3-b]naphtho-4,9-dione system.
    Author: Gomez-Monterrey I, Santelli G, Campiglia P, Califano D, Falasconi F, Pisano C, Vesci L, Lama T, Grieco P, Novellino E.
    Journal: J Med Chem; 2005 Feb 24; 48(4):1152-7. PubMed ID: 15715481.
    Abstract:
    The synthesis and cytotoxic evaluation of 3-(alkyl)(alkyl-substituted)spiro[(dihydroimidazo-2,4-dione)-5,3'-(2',3'-dihydrothieno[2,3-b]naphtho-4',9'-dione)]derivatives are described. Evaluation of these analogues against the MCF-7 human breast carcinoma and SW 620 human colon carcinoma cell lines uncovered for most of the compounds a cytotoxic potency comparable to or greater than that of doxorubicin. Compound 15 exhibited remarkable cytotoxic activity against several other human solid tumor cell lines. Interestingly, only a partial cross-resistance to compound 15 in selected tumor cell sublines known to be resistant to doxorubicin (MCF-7/Dx and A2780/Dx) was observed, whereas a total absence of cross-resistance in a tumor cell subline selected for resistance to cisplatin was found (A2780/DDP).
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