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

Authors :
Martín-Encinas, Endika
Rubiales, Gloria
Knudsen, Birgitta R.
Palacios, Francisco
Alonso, Concepción
Source :
Bioorganic & Medicinal Chemistry. Jun2021, Vol. 40, pN.PAG-N.PAG. 1p.
Publication Year :
2021

Abstract

[Display omitted] 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
09680896
Volume :
40
Database :
Academic Search Index
Journal :
Bioorganic & Medicinal Chemistry
Publication Type :
Academic Journal
Accession number :
150521869
Full Text :
https://doi.org/10.1016/j.bmc.2021.116177