School of Pharmacy, Lanzhou University, Lanzhou 730000, China.
Bioorg Med Chem. 2013 Nov 15;21(22):6948-55. doi: 10.1016/j.bmc.2013.09.026. Epub 2013 Sep 18.
A series of 4β-amino-4'-O-demethyl-4-deoxypodophyllotoxin derivatives were synthesized, and their cytotoxicities against several human cancer cell lines, including HepG2, A549, HeLa and HCT-8 cells, evaluated. Some of these compounds exhibited higher levels of cytotoxicity than the anticancer drug etoposide. 4β-N-(4-Nitrophenyl piperazinyl)-4'-O-demethyl-4-deoxypodophyllotoxin (11) was found to be the most potent synthesized compound in the current study, and induced cell cycle arrest in the G2/M phase in HeLa cells, which was accompanied by apoptosis. Furthermore, this compound activated the expression of cdc2, cyclin B1, p53 and caspase-3 in HeLa cells, leading to changes in the conformation of calf thymus DNA from the B-form to a more compact C-form.
合成了一系列 4β-氨基-4′-O-去甲-4-去氧鬼臼毒素衍生物，并评估了它们对包括 HepG2、A549、HeLa 和 HCT-8 细胞在内的几种人癌细胞系的细胞毒性。其中一些化合物的细胞毒性比抗癌药物依托泊苷更高。在本研究中，发现 4β-N-(4-硝基苯基哌嗪基)-4′-O-去甲-4-去氧鬼臼毒素（11）是合成的最有效化合物，可诱导 HeLa 细胞中的细胞周期停滞在 G2/M 期，并伴有细胞凋亡。此外，该化合物可激活 HeLa 细胞中 cdc2、cyclin B1、p53 和 caspase-3 的表达，导致小牛胸腺 DNA 构象从 B 型转变为更紧凑的 C 型。
