Synthesis and evaluation of aroylthiourea derivatives of 4-β-amino-4'-O-demethyl-4-desoxypodophyllotoxin as novel topoisomerase II inhibitors

A novel series of aroylthiourea derivatives of 4-β-amino-4′-O-demethyl-4-desoxy- podophyllotoxin were synthesized. Their cytotoxicities against three cancer cell lines were investigated by MTT assay. The kDNA decatenation assay indicated that compounds 5a, 5f, 5h and 5l inhibited topoisomerase II-mediated kDNA decatenation. DNA flow cytometric analysis revealed that compound 5a induced cell cycle arrest at G2/M phase in HCT-116 cell line. A novel series of aroylthiourea derivatives of 4-β-amino-4′-O-demethyl-4-desoxy- podophyllotoxin were synthesized. Their effect on human DNA topoisomerase II and antiproliferative activity was evaluated. [Display omitted] ► A series of aroylthiourea derivatives of 4-β-amino-4′-O-demethyl-4-desoxy- podophyllotoxin as novel topoisomerase II Inhibitors were designed and synthesized. Their cytotoxicities and topoisomerase II inhibitory activity were investigated.