Gu Wen, Jin Xiao-Yan, Li Dong-Dong, Wang Shi-Fa, Tao Xu-Bing, Chen Hao
Jiangsu Key Lab of Biomass-based Green Fuels and Chemicals, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, PR China.
Jiangsu Key Lab of Biomass-based Green Fuels and Chemicals, College of Chemical Engineering, Nanjing Forestry University, Nanjing 210037, PR China.
Bioorg Med Chem Lett. 2017 Sep 1;27(17):4128-4132. doi: 10.1016/j.bmcl.2017.07.033. Epub 2017 Jul 12.
A series of new quinoline derivatives of ursolic acid were designed and synthesized in an attempt to develop potential anticancer agents. The structures of these compounds were identified by H NMR, C NMR, IR and ESI-MS spectra analysis. The target compounds were evaluated for their in vitro cytotoxicity against three human cancer cell lines (MDA-MB-231, Hela and SMMC-7721). From the results, compounds 3a-d displayed significant antitumor activity against three cancer cell lines. Especially, compound 3b was found to be the most potent derivative with IC values of 0.61±0.07, 0.36±0.05, 12.49±0.08μM against MDA-MB-231, HeLa and SMMC-7721 cells, respectively, stronger than positive control etoposide. Furthermore, the Annexin V-FITC/PI dual staining assay revealed that compound 3b could significantly induce the apoptosis of MDA-MB-231 cells in a dose-dependent manner. The cell cycle analysis also indicated that compound 3b could cause cell cycle arrest of MDA-MB-231 cells at G0/G1 phase.
为了开发潜在的抗癌药物，设计并合成了一系列新的熊果酸喹啉衍生物。通过氢核磁共振（¹H NMR）、碳核磁共振（¹³C NMR）、红外光谱（IR）和电喷雾电离质谱（ESI-MS）分析确定了这些化合物的结构。评估了目标化合物对三种人类癌细胞系（MDA-MB-231、Hela和SMMC-7721）的体外细胞毒性。结果表明，化合物3a-d对三种癌细胞系均表现出显著的抗肿瘤活性。特别是，发现化合物3b是最有效的衍生物，对MDA-MB-231、HeLa和SMMC-7721细胞的半数抑制浓度（IC）值分别为0.61±0.07、0.36±0.05、12.49±0.08μM，比阳性对照依托泊苷更强。此外，膜联蛋白V-异硫氰酸荧光素/碘化丙啶（Annexin V-FITC/PI）双染法显示，化合物3b能以剂量依赖的方式显著诱导MDA-MB-231细胞凋亡。细胞周期分析还表明，化合物3b可使MDA-MB-231细胞在G0/G1期发生细胞周期阻滞。
