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

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

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: francisco.palacios@ehu.es.
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.

Figures