College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 609-735, Republic of Korea.
Bioorg Med Chem Lett. 2011 Oct 1;21(19):5730-4. doi: 10.1016/j.bmcl.2011.08.016. Epub 2011 Aug 18.
On the basis of the chemical structures of psorospermin with a xanthone template and acronycine derivatives with an acridone template, rac-1 and rac-2 constructed on an 1,2-dihydrobenzofuro[4,5-b][1,8]naphthyridin-6(11H)-one scaffold were designed and synthesized as potential anticancer agents. Their anticancer activities were evaluated against five human cancer cell lines. Rac-2 showed similar anticancer activity to doxorubicin and rac-1 exhibited even higher anticancer activity against LNCaP (IC(50)=0.14 μM), DU145 (IC(50)=0.15 μM), PC3 (IC(50)=0.30 μM) and MCF-7 (IC(50)=0.26 μM) cancer lines than doxorubicin and rac-2. Also, rac-1 revealed very potent anticancer activity (IC(50)=0.15 μM) against MCF-7/ADR cell (doxorubicin-resistant breast cancer cell) lines and induced G2/M phase arrest of the cell cycle in MCF-7/ADR cells.
基于 psorospermin（一种黄烷酮模板）和 acronycine 衍生物（一种吖啶酮模板）的化学结构，rac-1 和 rac-2 构建在 1,2-二氢苯并呋喃[4,5-b][1,8]萘啶-6(11H)-酮骨架上，被设计并合成作为潜在的抗癌药物。它们对五种人类癌细胞系的抗癌活性进行了评估。Rac-2 显示出与阿霉素相似的抗癌活性，而 rac-1 对 LNCaP（IC（50）=0.14 μM）、DU145（IC（50）=0.15 μM）、PC3（IC（50）=0.30 μM）和 MCF-7（IC（50）=0.26 μM）癌细胞系的抗癌活性甚至更高，优于阿霉素和 rac-2。此外，rac-1 对 MCF-7/ADR 细胞（多柔比星耐药乳腺癌细胞）系表现出非常强的抗癌活性（IC（50）=0.15 μM），并诱导 MCF-7/ADR 细胞的细胞周期 G2/M 期阻滞。
