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

► Three classes of 4β-Anilino-4′-O-demethyl-4-desoxypodophyllotoxin derivatives were designed and synthesized with the aim to improve the antiproliferative activity of etoposide as well as the drug-resistance profile. ► Most target compounds were identified as potent antitumor agents and showed improved activities comparing with their parent compound. ► Compound 26c exhibited as a promising agent that can be orally administered, and at 50 mg/kg it significantly inhibited high metastatic human lung cancer growth.