Yang Liu, Nan Xiang, Li Wen-Qun, Wang Mei-Juan, Zhao Xiao-Bo, Liu Ying-Qian, Zhang Zhi-Jun, Lee Kuo-Hsiung
Environmental and Municipal Engineering School, Lanzhou, Jiaotong University, Lanzhou 730000, People's Republic of China.
School of Pharmacy, Lanzhou University, Lanzhou 730000, People's Republic of China.
Med Chem Res. 2014 Nov;23(11):4926-4931. doi: 10.1007/s00044-014-1042-9.
A series of novel spin-labeled 4β-[(4-substituted)-1,2,3-triazol-1-yl]podophyllotoxin derivatives (-) were firstly designed and synthesized with significant regioselectivity by employing Cu(I) catalyzed click approach, and evaluated for cytotoxicity against four human tumor cell lines (A-549, DU145, KB, and KBvin). Among them, compound displayed the highest cytotoxic activity against the tumor cell lines tested. Significantly, compound showed superior cytotoxic activity compared with etoposide (IC 6.30 to>10 μM), a clinically available anticancer drug. Significant activity toward the drug resistant KBvin cell line revealed promising future for compound as a new generation of epipodophyllotoxin-derived antitumor clinical trial candidate.
首先采用铜（I）催化的点击方法，以显著的区域选择性设计并合成了一系列新型自旋标记的4β-[(4-取代)-1,2,3-三唑-1-基]鬼臼毒素衍生物（-），并评估了其对四种人类肿瘤细胞系（A-549、DU145、KB和KBvin）的细胞毒性。其中，化合物对所测试的肿瘤细胞系表现出最高的细胞毒性活性。值得注意的是，与临床上可用的抗癌药物依托泊苷（IC 6.30至>10 μM）相比，化合物表现出优异的细胞毒性活性。对耐药KBvin细胞系的显著活性揭示了化合物作为新一代鬼臼毒素衍生的抗肿瘤临床试验候选药物的广阔前景。
