Synthesis and evaluation of the cell cycle arrest and CT DNA interaction properties of 4β-amino-4'-O-demethyl-4-deoxypodophyllotoxins

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.