Design, synthesis and biological evaluation of 3-nitro-1,8-naphthalimides as potential antitumor agents

Bioorg Med Chem Lett. 2020 Apr 15;30(8):127051. doi: 10.1016/j.bmcl.2020.127051. Epub 2020 Feb 19.

Abstract

A series of 3-nitro-naphthalimides 1(1a-1h) were designed and synthesized as antitumor agents. MTT assay results showed that all these compounds exhibited obvious antiproliferative activity against SKOV3, HepG2, A549, T-24 and SMMC-7721 cancer cell lines, while compound 1a displayed the best antiproliferative activity against HepG2 and T-24 cell lines in comparison with mitonafide, with IC50 of 9.2 ± 1.8 and 4.133 ± 0.9 μM, respectively. In vivo antiproliferative activity assay results showed that compound 1a exhibited good antiproliferative activity in the HepG2 and T-24 models, compared with mitonafide. Action mechanism results showed that compound 1a could induced the damage of DNA and the inhibition topo I, accompanying by inducing the G2-stage arresting and the apoptosis of T-24 cancer cells through up-regulating expression levels of cyclin B1, cdc 2-pTy, Wee1, γH2AX, p21, Bax and cytochrome c and down-regulating expression of Bcl-2.

Keywords: 3-Nitro naphthalimides; Antitumor activity; Cell cycle arrest and apoptosis; DNA damage; Topo I.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Humans
  • Liver Neoplasms, Experimental / drug therapy
  • Liver Neoplasms, Experimental / pathology
  • Mice
  • Molecular Structure
  • Naphthalimides / chemistry
  • Naphthalimides / pharmacology*
  • Structure-Activity Relationship

Substances

  • 3-nitro-naphthalimide
  • Antineoplastic Agents
  • Naphthalimides