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

摘要

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).