Gomez-Monterrey Isabel, Santelli Giovanni, Campiglia Pietro, Califano Daniela, Falasconi Fabiano, Pisano Claudio, Vesci Loredana, Lama Teresa, Grieco Paolo, Novellino Ettore
Dipartimento di Chimica Farmaceutica e Tossicologica, University of Naples Federico II, Napoli, Italy.
J Med Chem. 2005 Feb 24;48(4):1152-7. doi: 10.1021/jm0408565.
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).
描述了3-(烷基)(烷基取代)螺[(二氢咪唑-2,4-二酮)-5,3'-(2',3'-二氢噻吩并[2,3-b]萘并-4',9'-二酮)]衍生物的合成及细胞毒性评估。对这些类似物针对MCF-7人乳腺癌和SW 620人结肠癌细胞系的评估发现，大多数化合物的细胞毒性效力与阿霉素相当或更强。化合物15对其他几种人实体瘤细胞系表现出显著的细胞毒性活性。有趣的是，在已知对阿霉素耐药（MCF-7/Dx和A2780/Dx）的选定肿瘤细胞亚系中，仅观察到对化合物15的部分交叉耐药性，而在选择对顺铂耐药的肿瘤细胞亚系（A2780/DDP）中则完全没有交叉耐药性。
