Synthesis and biological evaluation of new 4β-anilino-4'-O-demethyl-4-desoxypodophyllotoxin derivatives as potential antitumor agents.

A series of new 4β-anilino-4′-O-demethyl-4-desoxypodophyllotoxin derivatives were prepared and evaluated for their cytotoxicities against four human cancer cell lines including KB, KB/VCR, A549 and 95D. Most compounds showed better growth-inhibition activities against tested cell lines than that of etoposide (VP-16). Preliminary structure–activity relationships (SARs) were concluded and it indicated that the side chains substituted at 4β position of podophyllotoxin significantly influenced the cytotoxic activity, especially for the drug resistance profile. In vivo studies of compound 26c on highly metastatic human lung cancer xenograft in nude mice showed that it can significantly inhibit tumor growth with administrating by oral route.