Novel substituted 1,8‐naphthyridines: Design, synthesis, radiolabeling, and evaluation of apoptosis and topoisomerase II inhibition

Abuzahra, Manar; Ahmed, Nesreen S.; Sarhan, Mona O.; Mahgoub, Shahenda; Abdelhameed, Ahmed; Zaghary, Wafaa A.

doi:10.1002/ardp.202300035

Cited by 2 publications

(1 citation statement)

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“…The antiproliferative activity of some 1,8-naphthyridines like voreloxin is believed that to be related to topoisomerase II inhibition [ 48 ]. Other 1,8-naphthyridines have been designed as topoisomerase II inhibitors, studying the intercalation with DNA and enzymes [ 49 , 50 ]. Given that none of the compounds tested in this work were inhibitors of topoisomerase IB, based on the existing literature they could be acting as inhibitors of DNA topoisomerase II.…”

Section: Discussionmentioning

confidence: 99%

Antileishmanial Effect of 1,5- and 1,8-Substituted Fused Naphthyridines

Melcón-Fernandez,

Martín-Encinas,

Palacios

et al. 2023

Molecules

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In the absence of a vaccine, there is a need to find new drugs for the treatment of neglected tropical diseases, such as leishmaniasis, that can overcome the many drawbacks of those currently used. These disadvantages include cost, the need to maintain a cold chain, the route of administration, the associated adverse effects and the generation of resistance. In this work we have evaluated the antileishmanial effect of 1,5- and 1,8-substituted fused naphthyridines through in vitro and ex vivo assays, using genetically modified axenic and intramacrophagic Leishmania infantum amastigotes. The toxicity of these compounds has been tested in the mammalian host cell using murine splenic macrophages, as well as in murine intestinal organoids (miniguts) in order to assess their potential for oral administration. The 1,8- derivatives showed greater leishmanicidal activity and the presence of a nitrogen atom in the fused ring to the naphthyridine was important to increase the activity of both types of molecules. The aromatization of the pyridine ring also had marked differences in the activity of the compounds.

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Section: Discussionmentioning

confidence: 99%

Antileishmanial Effect of 1,5- and 1,8-Substituted Fused Naphthyridines

Melcón-Fernandez,

Martín-Encinas,

Palacios

et al. 2023

Molecules

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Novel 1,8-Naphthalimide Derivatives Inhibit Growth and Induce Apoptosis in Human Glioblastoma

Lee,

Chang,

Huang

et al. 2024

IJMS

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Given the rapid advancement of functional 1,8-Naphthalimide derivatives in anticancer research, we synthesized these two novel naphthalimide derivatives with diverse substituents and investigated the effect on glioblastoma multiforme (GBM) cells. Cytotoxicity, apoptosis, cell cycle, topoisomerase II and Western blotting assays were evaluated for these compounds against GBM in vitro. A human GBM xenograft mouse model established by subcutaneously injecting U87-MG cells and the treatment responses were assessed. Both compounds 3 and 4 exhibited significant antiproliferative activities, inducing apoptosis and cell death. Only compound 3 notably induced G2/M phase cell cycle arrest in the U87-MG GBM cells. Both compounds inhibited DNA topoisomerase II activity, resulting in DNA damage. The in vivo antiproliferative potential of compound 3 was further validated in a U87-MG GBM xenograft mouse model, without any discernible loss of body weight or kidney toxicity noted. This study presents novel findings demonstrating that 1,8-Naphthalimide derivatives exhibited significant GBM cell suppression in vitro and in vivo without causing adverse effects on body weight or kidney function. Further experiments, including investigations into mechanisms and pathways, as well as preclinical studies on the pharmacokinetics and pharmacodynamics, may be instrumental to the development of a new anti-GBM compound.

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Novel substituted 1,8‐naphthyridines: Design, synthesis, radiolabeling, and evaluation of apoptosis and topoisomerase II inhibition

Cited by 2 publications

References 50 publications

Antileishmanial Effect of 1,5- and 1,8-Substituted Fused Naphthyridines

Antileishmanial Effect of 1,5- and 1,8-Substituted Fused Naphthyridines

Novel 1,8-Naphthalimide Derivatives Inhibit Growth and Induce Apoptosis in Human Glioblastoma

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