Synthesis and biological evaluation of indeno[1,5]naphthyridines as topoisomerase I (TopI) inhibitors with antiproliferative activity

Eur J Med Chem. 2016 Jun 10:115:179-90. doi: 10.1016/j.ejmech.2016.03.031. Epub 2016 Mar 14.

Abstract

In an effort to establish new candidates with improved anticancer activity, we report here the synthesis of various series of 7H-indeno[2,1-c][1,5]-naphthyridines and novel 7H-indeno[2,1-c][1,5]-naphthyridine-7-ones and 7H-indeno[2,1-c][1,5]-naphthyridine-7-ols. Most of the products which were synthesized were able to inhibit Topoisomerase I activity. Moreover, in vitro testing demonstrated that a subset of the products exhibited a cytotoxic effect on cell lines derived from human breast cancer (BT 20), human lung adenocarcinoma (A 549), or human ovarian carcinoma (SKOV3).

Keywords: Antiproliferative effect; Enzyme inhibition; Topoisomerase I; [1,5]-Naphthyridines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Topoisomerases, Type I / metabolism*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Naphthyridines / chemical synthesis
  • Naphthyridines / chemistry
  • Naphthyridines / pharmacology*
  • Structure-Activity Relationship
  • Topoisomerase I Inhibitors / chemical synthesis*
  • Topoisomerase I Inhibitors / chemistry
  • Topoisomerase I Inhibitors / pharmacology*

Substances

  • Antineoplastic Agents
  • Naphthyridines
  • Topoisomerase I Inhibitors
  • indeno(1,5)naphthyridine
  • DNA Topoisomerases, Type I