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Volume 21, Issue 15
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

In recent years, as the biological activity of the quinoxaline skeleton has been revealed in numerous studies, interest in synthesizing new prototype molecules for the treatment of many chronic diseases, especially cancer, has increased.

Methods

The desired alkoxy substituted aminoquinoxalines () were synthesized by the reaction of and alkoxy substituted aryl amines such as 2-methoxyaniline, 4-methoxyaniline, 2-ethoxyaniline, 3-ethoxyaniline, 4-ethoxyaniline, 4-butoxyaniline, 2,4-dimethoxyaniline, 3,4-dimethoxyaniline, and 3,5-dimethoxyaniline according to the previously published procedure. was aminated in DMSO at 130°C. We synthesized various alkoxy substituted aminoquinoxaline compounds () and evaluated their anticancer and antimicrobial activities in order to expand the search to related structures. In particular, two aminoquinoxaline ( and ) compounds, coded as NSC D-835971/1 and NSC D-835972/1 by the National Cancer Institute in the USA, were screened for anticancer screening at a dose of 10-5 M on a full panel of 60 human cell lines obtained from nine human cancer cell types (leukemia, melanoma, non-small cell lung, colon, central nervous system, ovarian, kidney, prostate, and breast cancer).

Results

Further studies were also conducted for the compound (NSC D-835971/1), which was found to be the most active antiproliferative agent, especially against leukemia cell lines. Molecular docking studies showed that interacted with Glu286 and Lys271 through hydrogen bonding and π-stacking interaction in the ATP binding region of Abl kinase, which is indicated as a potential target of leukemia. Besides, occupied the minor groove of the double helix of DNA π-stacking interaction with DG-6.

Conclusion

According to pharmacokinetic determination, was endowed with drug-like properties as a potential anticancer drug candidate for future experiments. In the light of these findings, more research will focus on aminated quinoxalines' ability to precisely target leukemia cancer cell lines.

© 2024 Bentham Science Publishers
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2024-01-09
2025-06-22

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Discovery of the Aminated Quinoxalines as Potential Active Molecules
Letters in Drug Design & Discovery 21, 3285 (2024); https://doi.org/10.2174/0115701808281517231215113741
/content/journals/lddd/10.2174/0115701808281517231215113741
/content/journals/lddd/10.2174/0115701808281517231215113741
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  • Article Type:     Research Article
Keyword(s): ADME; Anticancer activity; antimicrobial activity; leukemia; molecular docking; quinoxalines

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