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  • Title: Synthesis and evaluation of the cell cycle arrest and CT DNA interaction properties of 4β-amino-4'-O-demethyl-4-deoxypodophyllotoxins.
    Author: Liu JF, Sang CY, Qin WW, Zhao J, Hui L, Ding YL, Chen SW.
    Journal: Bioorg Med Chem; 2013 Nov 15; 21(22):6948-55. PubMed ID: 24095019.
    Abstract:
    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.
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