Synthesis and Cytotoxic Evaluation of Novel Spirohydantoin Derivatives of the Dihydrothieno[2,3-b]naphtho-4,9-dione System

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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