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Fused chromeno and quinolino[1,8]naphthyridines: Synthesis and biological evaluation as topoisomerase I inhibitors and antiproliferative agents

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  • Endika Martín-Encinas, Universidad del Pais Vasco
  • ,
  • Gloria Rubiales, Universidad del Pais Vasco
  • ,
  • Birgitta R. Knudsen
  • Francisco Palacios, Universidad del Pais Vasco
  • ,
  • Concepción Alonso, Universidad del Pais Vasco

The synthesis of 1,8-naphthyridine derivatives fused with other heterocycles, such as chromenes and quinolines, as well as their behaviour as topoisomerase I inhibitors is studied. The preparation is carried out through a direct and simple process as an intramolecular [4 + 2] cycloaddition reaction between functionalized aldimines, obtained by the condensation of 2-aminopyridine and unsaturated aldehydes, and olefins. In particular, while no clear inhibitory activity is observed for chromeno[4,3-b][1,8]naphthyridine fused heterocycles, a very different result is observed for quinolino[4,3-b][1,8]naphthyridine derivatives. Experimental assays indicated that quinolino[4,3-b][1,8]naphthyridines inhibited the topoisomerase I enzymatic reaction behaving like a poison, as occurs with the natural TopI inhibitor, camptothecin. Furthermore, the cytotoxic effect on cell lines derived from human lung adenocarcinoma (A549), human ovarian carcinoma (SKOV3), and on non-cancerous lung fibroblasts cell line (MRC5) was also screened.

Original languageEnglish
Article number116177
JournalBioorganic and Medicinal Chemistry
Publication statusPublished - Jun 2021

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Ltd

    Research areas

  • Antiproliferative effect, Enzyme inhibition, Intramolecular [4+2]-cycloaddition, Naphthyridines, Topoisomerase I

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