Synthesis and biological evaluation of novel alkylated polyamine analogues as potential anticancer agents

摘要

Abstract A new class of polyamine analogues modified by alkylation at the terminal of the polyamine chain has been synthesized and their structures were determined by 1 H NMR, 13 C NMR, ESI-MS and elemental analysis. As the representative compound, 3f displayed a broad spectrum of anti-cancer effects by MTT assays. Tumor xenograft model and pulmonary metastasis model showed that compound 3f significantly suppressed tumor growth and metastasis in?vivo , which was more stronger than the reference drug amonafide. Molecular mechanisms indicated that compound 3f exhibited antiproliferative activities and induced the generation of reactive oxygen species (ROS), which resulted in the occurrence of autophagy. The downregulated expression of MMP-9 and β-catenin by compound 3f accounted for the inhibition of migration. Taken altogether, the in?vitro and in?vivo biological evaluations corroborated compound 3f to be an effective anticancer agent. Graphical abstract Novel alkylated naphthalimide-polyamine analogues were synthesized and their antitumor activities were investigated, compound 3f induced ROS-mediated autophagy, proliferation and suppressed migration, resulting in the inhibition of tumor growth and metastasis. Display Omitted Highlights ? Ten naphthalimide-polyamine conjugates modified terminally by alkyl groups were synthesized. ? Compound 3f suppressed cancer cell proliferation and migration in?vitro. ? Compound 3f inhibited tumor growth and pulmonary metastasis in?vivo. ? Reactive oxygen species (ROS) in hepatoma cells were induced after compound 3f treatment. ? Compound 3f -induced autophagy was dependent on ROS generation.