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.
Concepción Alonso  1 ,  María Fuertes  1 ,  María González  1 ,  Gloria Rubiales  1 ,  Cinzia Tesauro  2 ,  Birgitta R Knudsen  2 ,  Francisco Palacios  3
Affiliations
  • 1. Departamento de Química Orgánica I, Facultad de Farmacia and Centro de Investigación Lascaray (Lascaray Research Center), Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU), Paseo de la Universidad 7, 01006, Vitoria-Gasteiz, Spain.
  • 2. Department of Molecular Biology and Genetics and Interdisciplinary Nanoscience Center (iNANO), Aarhus University, Aarhus, 8000, Denmark.
  • 3. Departamento de Química Orgánica I, Facultad de Farmacia and Centro de Investigación Lascaray (Lascaray Research Center), Universidad del País Vasco/Euskal Herriko Unibertsitatea (UPV/EHU), Paseo de la Universidad 7, 01006, Vitoria-Gasteiz, Spain. Electronic address: [email protected].
PMID: 27017547 DOI: 10.1016/j.ejmech.2016.03.031
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.