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.
Mao Xin  1 ,  Jian-Hua Wei  1 ,  Chen-Hui Yang  1 ,  Gui-Bin Liang  1 ,  Dan Su  1 ,  Xian-Li Ma  2 ,  Ye Zhang  3
Affiliations
  • 1. School of Pharmacy, Guilin Medical University, Guilin 541004, China.
  • 2. School of Pharmacy, Guilin Medical University, Guilin 541004, China. Electronic address: [email protected].
  • 3. School of Pharmacy, Guilin Medical University, Guilin 541004, China; Department of Chemistry & Pharmaceutical Science, Guilin Normal College, Guangxi 541001, China. Electronic address: [email protected].
PMID: 32111436 DOI: 10.1016/j.bmcl.2020.127051
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.
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