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Synthesis and cytotoxic evaluation of some novel quinoxalinedione diarylamide sorafenib analogues

A series of novel sorafenib analogues containing a quinoxalinedione ring and amide linker were synthesized. A total of 9 novel compounds in 6 synthetic steps were synthesized. Briefly, the amino group of p-aminophenol was first protected which then followed by O-arylation with 5-chloro-2-nitroanilin...

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Autores principales: Khandan, Mojtaba, Sadeghian-Rizi, Sedighe, Khodarahmi, Ghadamali, Hassanzadeh, Farshid
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Medknow Publications & Media Pvt Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842488/
https://www.ncbi.nlm.nih.gov/pubmed/29606971
http://dx.doi.org/10.4103/1735-5362.223802
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author Khandan, Mojtaba
Sadeghian-Rizi, Sedighe
Khodarahmi, Ghadamali
Hassanzadeh, Farshid
author_facet Khandan, Mojtaba
Sadeghian-Rizi, Sedighe
Khodarahmi, Ghadamali
Hassanzadeh, Farshid
author_sort Khandan, Mojtaba
collection PubMed
description A series of novel sorafenib analogues containing a quinoxalinedione ring and amide linker were synthesized. A total of 9 novel compounds in 6 synthetic steps were synthesized. Briefly, the amino group of p-aminophenol was first protected which then followed by O-arylation with 5-chloro-2-nitroaniline to provide compound d. Reduction of the nitro group of compound d and cyclization of the diamine group of compound e with oxalic acid afforded compound f which on deacetylation yeilded compound g. Then compound g was reacted with different acyl halides to afford the target compounds 1h-1p. Chemical structures of synthesized compounds were confirmed by 1H NMR and FT-IR analysis. All compounds were evaluated at 1, 10, 50 and 100 μM concentrations for their cytotoxicity against HeLa and MCF-7 cancer cell lines. Some of the compounds showed good cytotoxic activity, especially compounds 1i and 1k-1n with the IC50 values of 19, 16, 22, 18, and 16 μM against MCF-7 cell line and 20, 18, 25, 20, and 18 μM against HeLa cell line, respectively.
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spelling pubmed-58424882018-04-01 Synthesis and cytotoxic evaluation of some novel quinoxalinedione diarylamide sorafenib analogues Khandan, Mojtaba Sadeghian-Rizi, Sedighe Khodarahmi, Ghadamali Hassanzadeh, Farshid Res Pharm Sci Original Article A series of novel sorafenib analogues containing a quinoxalinedione ring and amide linker were synthesized. A total of 9 novel compounds in 6 synthetic steps were synthesized. Briefly, the amino group of p-aminophenol was first protected which then followed by O-arylation with 5-chloro-2-nitroaniline to provide compound d. Reduction of the nitro group of compound d and cyclization of the diamine group of compound e with oxalic acid afforded compound f which on deacetylation yeilded compound g. Then compound g was reacted with different acyl halides to afford the target compounds 1h-1p. Chemical structures of synthesized compounds were confirmed by 1H NMR and FT-IR analysis. All compounds were evaluated at 1, 10, 50 and 100 μM concentrations for their cytotoxicity against HeLa and MCF-7 cancer cell lines. Some of the compounds showed good cytotoxic activity, especially compounds 1i and 1k-1n with the IC50 values of 19, 16, 22, 18, and 16 μM against MCF-7 cell line and 20, 18, 25, 20, and 18 μM against HeLa cell line, respectively. Medknow Publications & Media Pvt Ltd 2018-04 /pmc/articles/PMC5842488/ /pubmed/29606971 http://dx.doi.org/10.4103/1735-5362.223802 Text en Copyright: © 2018 Research in Pharmaceutical Sciences http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
spellingShingle Original Article
Khandan, Mojtaba
Sadeghian-Rizi, Sedighe
Khodarahmi, Ghadamali
Hassanzadeh, Farshid
Synthesis and cytotoxic evaluation of some novel quinoxalinedione diarylamide sorafenib analogues
title Synthesis and cytotoxic evaluation of some novel quinoxalinedione diarylamide sorafenib analogues
title_full Synthesis and cytotoxic evaluation of some novel quinoxalinedione diarylamide sorafenib analogues
title_fullStr Synthesis and cytotoxic evaluation of some novel quinoxalinedione diarylamide sorafenib analogues
title_full_unstemmed Synthesis and cytotoxic evaluation of some novel quinoxalinedione diarylamide sorafenib analogues
title_short Synthesis and cytotoxic evaluation of some novel quinoxalinedione diarylamide sorafenib analogues
title_sort synthesis and cytotoxic evaluation of some novel quinoxalinedione diarylamide sorafenib analogues
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5842488/
https://www.ncbi.nlm.nih.gov/pubmed/29606971
http://dx.doi.org/10.4103/1735-5362.223802
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