TY - JOUR
T1 - Fused chromeno and quinolino[1,8]naphthyridines
T2 - Synthesis and biological evaluation as topoisomerase I inhibitors and antiproliferative agents
AU - Martín-Encinas, Endika
AU - Rubiales, Gloria
AU - Knudsen, Birgitta R.
AU - Palacios, Francisco
AU - Alonso, Concepción
N1 - Publisher Copyright:
© 2021 Elsevier Ltd
PY - 2021/6
Y1 - 2021/6
N2 - 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.
AB - 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.
KW - Antiproliferative effect
KW - Enzyme inhibition
KW - Intramolecular [4+2]-cycloaddition
KW - Naphthyridines
KW - Topoisomerase I
UR - http://www.scopus.com/inward/record.url?scp=85105307615&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2021.116177
DO - 10.1016/j.bmc.2021.116177
M3 - Journal article
C2 - 33962152
AN - SCOPUS:85105307615
SN - 0968-0896
VL - 40
JO - Bioorganic and Medicinal Chemistry
JF - Bioorganic and Medicinal Chemistry
M1 - 116177
ER -