【文章名】Spiro[(dihydropyrazin-2,5-dione)-6,3'-(2',3'-dihydrothieno[2,3-b]naphtho -4',9'-dione)]-Based Cytotoxic Agents: Structure-Activity Relationship Studies on the Substituent at N4-Position of the Diketopiperazine Domain.
Spiro[(dihydropyrazin-2,5-dione)-6,3'-(2',3'-dihydrothieno[2,3-b]naphtho -4',9'-dione)]-Based Cytotoxic Agents: Structure-Activity Relationship Studies on the Substituent at N4-Position of the Diketopiperazine Domain.
[摘要]：Analogs of the previously reported potent cytotoxic spiro[(dihydropyrazine-2,5-dione)-6,3'-(2',3'-dihydrothieno[2,3-b]naphth o-4',9'-dione)] derivs. were prepd. to explore new structural requirements at the diketopiperazine domain for the cytotoxic activity. The in vitro activity was evaluated against the MCF-7 human breast carcinoma and SW 620 human colon carcinoma cell lines. The 4-[(2-N,N-dimethyl)amino]ethyl (I, R = CH2CH2NMe2), and the 4-(2-pyrrolidinoethyl) (I, R = 2-pyrrolidinoethyl) derivs. emerged as the most potent compds. of this series, with a cytotoxic activity comparable to that of doxorubicin. These compds., in both racemic and pure enantiomeric forms, showed also a high efficacy in cell lines resistant to doxorubicin (MCF-7/Dx) and in cell lines that were highly resistant to treatment with doxorubicin, such as HEK-293 (kidney), M-14 (melanoma), and HeLa (cervical adenocarcinoma) human cell lines. In addn., the effects on growth and cell cycle progression in CaCo-2 cell line (colon adenocarcinoma) and DNA-binding properties were investigated.
