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Straightforward synthesis and biological evaluation as topoisomerase I inhibitors and antiproliferative agents of hybrid Chromeno[4,3-b][1,5]Naphthyridines and Chromeno[4,3-b][1,5]Naphthyridin-6-ones

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Straightforward synthesis and biological evaluation as topoisomerase I inhibitors and antiproliferative agents of hybrid Chromeno[4,3-b][1,5]Naphthyridines and Chromeno[4,3-b][1,5]Naphthyridin-6-ones. / Martín-Encinas, Endika; Rubiales, Gloria; Knudssen, Birgitta R. et al.
In: European Journal of Medicinal Chemistry, Vol. 178, 09.2019, p. 752-766.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Harvard

Martín-Encinas, E, Rubiales, G, Knudssen, BR, Palacios, F & Alonso, C 2019, 'Straightforward synthesis and biological evaluation as topoisomerase I inhibitors and antiproliferative agents of hybrid Chromeno[4,3-b][1,5]Naphthyridines and Chromeno[4,3-b][1,5]Naphthyridin-6-ones', European Journal of Medicinal Chemistry, vol. 178, pp. 752-766. https://doi.org/10.1016/j.ejmech.2019.06.032

APA

Martín-Encinas, E., Rubiales, G., Knudssen, B. R., Palacios, F., & Alonso, C. (2019). Straightforward synthesis and biological evaluation as topoisomerase I inhibitors and antiproliferative agents of hybrid Chromeno[4,3-b][1,5]Naphthyridines and Chromeno[4,3-b][1,5]Naphthyridin-6-ones. European Journal of Medicinal Chemistry, 178, 752-766. https://doi.org/10.1016/j.ejmech.2019.06.032

CBE

Martín-Encinas E, Rubiales G, Knudssen BR, Palacios F, Alonso C. 2019. Straightforward synthesis and biological evaluation as topoisomerase I inhibitors and antiproliferative agents of hybrid Chromeno[4,3-b][1,5]Naphthyridines and Chromeno[4,3-b][1,5]Naphthyridin-6-ones. European Journal of Medicinal Chemistry. 178:752-766. https://doi.org/10.1016/j.ejmech.2019.06.032

MLA

Martín-Encinas, Endika et al. "Straightforward synthesis and biological evaluation as topoisomerase I inhibitors and antiproliferative agents of hybrid Chromeno[4,3-b][1,5]Naphthyridines and Chromeno[4,3-b][1,5]Naphthyridin-6-ones". European Journal of Medicinal Chemistry. 2019, 178. 752-766. https://doi.org/10.1016/j.ejmech.2019.06.032

Vancouver

Martín-Encinas E, Rubiales G, Knudssen BR, Palacios F, Alonso C. Straightforward synthesis and biological evaluation as topoisomerase I inhibitors and antiproliferative agents of hybrid Chromeno[4,3-b][1,5]Naphthyridines and Chromeno[4,3-b][1,5]Naphthyridin-6-ones. European Journal of Medicinal Chemistry. 2019 Sept;178:752-766. doi: 10.1016/j.ejmech.2019.06.032

Author

Martín-Encinas, Endika ; Rubiales, Gloria ; Knudssen, Birgitta R. et al. / Straightforward synthesis and biological evaluation as topoisomerase I inhibitors and antiproliferative agents of hybrid Chromeno[4,3-b][1,5]Naphthyridines and Chromeno[4,3-b][1,5]Naphthyridin-6-ones. In: European Journal of Medicinal Chemistry. 2019 ; Vol. 178. pp. 752-766.

Bibtex

@article{4628826911354f818498cd9a3f626855,
title = "Straightforward synthesis and biological evaluation as topoisomerase I inhibitors and antiproliferative agents of hybrid Chromeno[4,3-b][1,5]Naphthyridines and Chromeno[4,3-b][1,5]Naphthyridin-6-ones",
abstract = "This work describes the synthesis of hybrid tetrahydro-1,5-naphthyridine and 1,5-naphthyridine derivatives fused with heterocycles such as chromenes and chromen-2-ones or coumarins, which were synthesized in good to high general yields. The synthetic route involves an intramolecular [4 + 2]-cycloaddition reaction of functionalized aldimines obtained by the condensation of 3-aminopyridine and aldehydes containing a double or triple carbon-carbon bond in orto position and allows the selective generation of three stereogenic centers in a short, efficient and reliable synthesis. The subsequent dehydrogenation of the fused tetrahydrochromeno[4,3-b][1,5]naphthyridines and/or tetrahydrochromeno[4,3-b][1,5]naphthyridin-6-ones leads to the formation of the corresponding tetracyclic chromeno[4,3-b][1,5]naphthyridine derivatives and/or chromeno[4,3-b][1,5]naphthyridin-6-ones in quantitative yields. Some of the prepared products showed activity as inhibitors of Topoisomerase I (TopI). Additionally, the cytotoxic behavior of these compounds has been studied in cell lines derived from human lung adenocarcinoma (A549) and human ovarian carcinoma (SKOV03), and on non-cancerous lung fibroblasts cell line (MRC5) where, on the last ones, the absence of cytotoxicity was observed. 7-Phenyl-6H-6a,7,12,12a-tetrahydrochromeno[4,3-b][1,5]naphthyridine 5a showed excellent cytotoxic activity with a IC50 value of 1.03 ± 0.30 μM against the A549 cell line and a IC50 value of 1.75 ± 0.20 μM against the SKOV03 cell line. The obtained results point to these compounds as good antiproliferative candidates.",
keywords = "Antiproliferative effect, chromeno[4,3-b][1,5]naphthyridin-6-ones, Chromeno[4,3-b][1,5]naphthyridines, Enzyme inhibition, Topoisomerase I",
author = "Endika Mart{\'i}n-Encinas and Gloria Rubiales and Knudssen, {Birgitta R.} and Francisco Palacios and Concepci{\'o}n Alonso",
year = "2019",
month = sep,
doi = "10.1016/j.ejmech.2019.06.032",
language = "English",
volume = "178",
pages = "752--766",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson",

}

RIS

TY - JOUR

T1 - Straightforward synthesis and biological evaluation as topoisomerase I inhibitors and antiproliferative agents of hybrid Chromeno[4,3-b][1,5]Naphthyridines and Chromeno[4,3-b][1,5]Naphthyridin-6-ones

AU - Martín-Encinas, Endika

AU - Rubiales, Gloria

AU - Knudssen, Birgitta R.

AU - Palacios, Francisco

AU - Alonso, Concepción

PY - 2019/9

Y1 - 2019/9

N2 - This work describes the synthesis of hybrid tetrahydro-1,5-naphthyridine and 1,5-naphthyridine derivatives fused with heterocycles such as chromenes and chromen-2-ones or coumarins, which were synthesized in good to high general yields. The synthetic route involves an intramolecular [4 + 2]-cycloaddition reaction of functionalized aldimines obtained by the condensation of 3-aminopyridine and aldehydes containing a double or triple carbon-carbon bond in orto position and allows the selective generation of three stereogenic centers in a short, efficient and reliable synthesis. The subsequent dehydrogenation of the fused tetrahydrochromeno[4,3-b][1,5]naphthyridines and/or tetrahydrochromeno[4,3-b][1,5]naphthyridin-6-ones leads to the formation of the corresponding tetracyclic chromeno[4,3-b][1,5]naphthyridine derivatives and/or chromeno[4,3-b][1,5]naphthyridin-6-ones in quantitative yields. Some of the prepared products showed activity as inhibitors of Topoisomerase I (TopI). Additionally, the cytotoxic behavior of these compounds has been studied in cell lines derived from human lung adenocarcinoma (A549) and human ovarian carcinoma (SKOV03), and on non-cancerous lung fibroblasts cell line (MRC5) where, on the last ones, the absence of cytotoxicity was observed. 7-Phenyl-6H-6a,7,12,12a-tetrahydrochromeno[4,3-b][1,5]naphthyridine 5a showed excellent cytotoxic activity with a IC50 value of 1.03 ± 0.30 μM against the A549 cell line and a IC50 value of 1.75 ± 0.20 μM against the SKOV03 cell line. The obtained results point to these compounds as good antiproliferative candidates.

AB - This work describes the synthesis of hybrid tetrahydro-1,5-naphthyridine and 1,5-naphthyridine derivatives fused with heterocycles such as chromenes and chromen-2-ones or coumarins, which were synthesized in good to high general yields. The synthetic route involves an intramolecular [4 + 2]-cycloaddition reaction of functionalized aldimines obtained by the condensation of 3-aminopyridine and aldehydes containing a double or triple carbon-carbon bond in orto position and allows the selective generation of three stereogenic centers in a short, efficient and reliable synthesis. The subsequent dehydrogenation of the fused tetrahydrochromeno[4,3-b][1,5]naphthyridines and/or tetrahydrochromeno[4,3-b][1,5]naphthyridin-6-ones leads to the formation of the corresponding tetracyclic chromeno[4,3-b][1,5]naphthyridine derivatives and/or chromeno[4,3-b][1,5]naphthyridin-6-ones in quantitative yields. Some of the prepared products showed activity as inhibitors of Topoisomerase I (TopI). Additionally, the cytotoxic behavior of these compounds has been studied in cell lines derived from human lung adenocarcinoma (A549) and human ovarian carcinoma (SKOV03), and on non-cancerous lung fibroblasts cell line (MRC5) where, on the last ones, the absence of cytotoxicity was observed. 7-Phenyl-6H-6a,7,12,12a-tetrahydrochromeno[4,3-b][1,5]naphthyridine 5a showed excellent cytotoxic activity with a IC50 value of 1.03 ± 0.30 μM against the A549 cell line and a IC50 value of 1.75 ± 0.20 μM against the SKOV03 cell line. The obtained results point to these compounds as good antiproliferative candidates.

KW - Antiproliferative effect

KW - chromeno[4,3-b][1,5]naphthyridin-6-ones

KW - Chromeno[4,3-b][1,5]naphthyridines

KW - Enzyme inhibition

KW - Topoisomerase I

UR - http://www.scopus.com/inward/record.url?scp=85067463273&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2019.06.032

DO - 10.1016/j.ejmech.2019.06.032

M3 - Journal article

C2 - 31229877

AN - SCOPUS:85067463273

VL - 178

SP - 752

EP - 766

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

ER -