%0 Journal Article
%T Synthesis of Thiophene and NO-Curcuminoids for Antiinflammatory and Anti-Cancer Activities
%A Mahera M. Ahmed
%A M. Akram Khan
%A Kim Drummond Rainsford
%J Molecules
%D 2013
%I MDPI AG
%R 10.3390/molecules18021483
%X In search of better NSAIDs four novel nitric oxide donating derivatives of curcumin (compounds 9a¨C d), and four thiophene curcuminoids (compounds 10a¨C 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-1¦Â, TNF-¦Á 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¨C d and the thiophene curcuminoids 10a¨C c and 11 were non-cytotoxic to THP-1 cells over a concentration range of 10-100 ¦ÌM 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 ¦ÌM, whereas 10a and 10c were non-cytotoxic at 10 ¦ÌM 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-¦Â production at their non-cytotoxic concentrations, whereas, they did not decrease TNF-¦Á production in CACO-2 cells. Compound 11 showed a significant decrease in CXCL-8 production.
%K NO-NSAIDs
%K synthesis
%K curcuminoids
%K cytotoxicity
%K cytokines
%K chemokines
%K anti-cancer
%U http://www.mdpi.com/1420-3049/18/2/1483