Cargando…

Synthesis of Thiophene and NO-Curcuminoids for Antiinflammatory and Anti-Cancer Activities

In search of better NSAIDs four novel nitric oxide donating derivatives of curcumin (compounds 9a–d), and four thiophene curcuminoids (compounds 10a–c, 11) have been synthesised. The cytotoxic effects of these compounds along with the lead compound curcumin (7) and their effect on the production of...

Descripción completa

Detalles Bibliográficos
Autores principales: Ahmed, Mahera M., Khan, M. Akram, Rainsford, Kim Drummond
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271105/
https://www.ncbi.nlm.nih.gov/pubmed/23353121
http://dx.doi.org/10.3390/molecules18021483
_version_ 1783376851973963776
author Ahmed, Mahera M.
Khan, M. Akram
Rainsford, Kim Drummond
author_facet Ahmed, Mahera M.
Khan, M. Akram
Rainsford, Kim Drummond
author_sort Ahmed, Mahera M.
collection PubMed
description In search of better NSAIDs four novel nitric oxide donating derivatives of curcumin (compounds 9a–d), and four thiophene curcuminoids (compounds 10a–c, 11) have been synthesised. The cytotoxic effects of these compounds along with the lead compound curcumin (7) and their effect on the production of the reactive oxygen species nitric oxide and pro-inflammatory cytokines IL-1β, TNF-α and chemokine CXCL-8 were evaluated using human monocytic THP-1 and colon adenocarcinoma CACO-2 cell lines. All of the nitric oxide donating curcuminoids 9a–d and the thiophene curcuminoids 10a–c and 11 were non-cytotoxic to THP-1 cells over a concentration range of 10-100 μM and compared with curcumin compounds 10b and 10c, were more toxic. In CACO-2 cells, 10b and 11 appeared to be non-toxic at 10 to 50 μM, whereas 10a and 10c were non-cytotoxic at 10 μM only. These results clearly indicate that the introduction of a nitroxybutyl moiety to curcumin and replacement of phenyl rings with thiophene units reduces the cytotoxic effect of the parent curcumin, whereas a methyl substituted thiophene increases the cytotoxic effects. In THP-1 cells, drugs 10a and 11 significantly decreased IL-1-β production at their non-cytotoxic concentrations, whereas, they did not decrease TNF-α production in CACO-2 cells. Compound 11 showed a significant decrease in CXCL-8 production.
format Online
Article
Text
id pubmed-6271105
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-62711052018-12-14 Synthesis of Thiophene and NO-Curcuminoids for Antiinflammatory and Anti-Cancer Activities Ahmed, Mahera M. Khan, M. Akram Rainsford, Kim Drummond Molecules Article In search of better NSAIDs four novel nitric oxide donating derivatives of curcumin (compounds 9a–d), and four thiophene curcuminoids (compounds 10a–c, 11) have been synthesised. The cytotoxic effects of these compounds along with the lead compound curcumin (7) and their effect on the production of the reactive oxygen species nitric oxide and pro-inflammatory cytokines IL-1β, TNF-α and chemokine CXCL-8 were evaluated using human monocytic THP-1 and colon adenocarcinoma CACO-2 cell lines. All of the nitric oxide donating curcuminoids 9a–d and the thiophene curcuminoids 10a–c and 11 were non-cytotoxic to THP-1 cells over a concentration range of 10-100 μM and compared with curcumin compounds 10b and 10c, were more toxic. In CACO-2 cells, 10b and 11 appeared to be non-toxic at 10 to 50 μM, whereas 10a and 10c were non-cytotoxic at 10 μM only. These results clearly indicate that the introduction of a nitroxybutyl moiety to curcumin and replacement of phenyl rings with thiophene units reduces the cytotoxic effect of the parent curcumin, whereas a methyl substituted thiophene increases the cytotoxic effects. In THP-1 cells, drugs 10a and 11 significantly decreased IL-1-β production at their non-cytotoxic concentrations, whereas, they did not decrease TNF-α production in CACO-2 cells. Compound 11 showed a significant decrease in CXCL-8 production. MDPI 2013-01-25 /pmc/articles/PMC6271105/ /pubmed/23353121 http://dx.doi.org/10.3390/molecules18021483 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Article
Ahmed, Mahera M.
Khan, M. Akram
Rainsford, Kim Drummond
Synthesis of Thiophene and NO-Curcuminoids for Antiinflammatory and Anti-Cancer Activities
title Synthesis of Thiophene and NO-Curcuminoids for Antiinflammatory and Anti-Cancer Activities
title_full Synthesis of Thiophene and NO-Curcuminoids for Antiinflammatory and Anti-Cancer Activities
title_fullStr Synthesis of Thiophene and NO-Curcuminoids for Antiinflammatory and Anti-Cancer Activities
title_full_unstemmed Synthesis of Thiophene and NO-Curcuminoids for Antiinflammatory and Anti-Cancer Activities
title_short Synthesis of Thiophene and NO-Curcuminoids for Antiinflammatory and Anti-Cancer Activities
title_sort synthesis of thiophene and no-curcuminoids for antiinflammatory and anti-cancer activities
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6271105/
https://www.ncbi.nlm.nih.gov/pubmed/23353121
http://dx.doi.org/10.3390/molecules18021483
work_keys_str_mv AT ahmedmaheram synthesisofthiopheneandnocurcuminoidsforantiinflammatoryandanticanceractivities
AT khanmakram synthesisofthiopheneandnocurcuminoidsforantiinflammatoryandanticanceractivities
AT rainsfordkimdrummond synthesisofthiopheneandnocurcuminoidsforantiinflammatoryandanticanceractivities