Division of Organic Chemistry, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500 607, India.
Bioorg Med Chem. 2012 Jan 15;20(2):789-800. doi: 10.1016/j.bmc.2011.12.003. Epub 2011 Dec 14.
A series of benzo[c,d]indol-2(1H)one-PBD conjugates (11a-l) have been designed and synthesized as potential anticancer agents. These compounds were prepared by linking the C8-position of DC-81 with a benzo[c,d]indol-2(1H)one moiety through different alkane spacers in good yields and confirmed by (1)H NMR, mass and HRMS data. The DNA binding ability of these conjugates was evaluated by thermal denaturation studies and interestingly, compound 11l showed enhanced DNA binding ability. These compounds were also evaluated for their anticancer activity in selected human cancer cell lines of lung, skin, colon and prostate by using MTT assay method. These new conjugates showed promising anticancer activity with IC(50) values ranging from 1.05 to 36.49 μM. Moreover, cell cycle arrest in SubG1 phase was observed upon treatment of A549 cells with 1 and 2 μM (IC(50)) concentrations of compound 11l and it induced apoptosis. This is confirmed by Annexin V-FITC, Hoechst staining, caspase-3 activity as well as DNA fragmentation analysis.
一系列苯并[c,d]吲哚-2(1H)酮-PBD 缀合物（11a-l）已被设计和合成，作为潜在的抗癌药物。这些化合物是通过将 DC-81 的 C8 位与不同的烷烃间隔物连接的苯并[c,d]吲哚-2(1H)酮部分合成的，产率良好，并通过（1）H NMR、质谱和高分辨质谱数据得到证实。这些缀合物的 DNA 结合能力通过热变性研究进行评估，有趣的是，化合物 11l 显示出增强的 DNA 结合能力。这些化合物还通过 MTT 测定法在选定的肺癌、皮肤癌、结肠癌和前列腺癌的人类癌细胞系中评估其抗癌活性。这些新的缀合物表现出有希望的抗癌活性，IC（50）值范围为 1.05 至 36.49 μM。此外，用 11l 化合物 1 和 2 μM（IC（50））浓度处理 A549 细胞时，观察到细胞周期停滞在 SubG1 期，并且诱导细胞凋亡。这通过 Annexin V-FITC、Hoechst 染色、caspase-3 活性以及 DNA 片段化分析得到证实。
