881916-06-9Relevant articles and documents
Thiazole derivatives as inhibitors of cyclooxygenases in vitro and in vivo
El-Achkar, Ghewa A.,Jouni, Mariam,Mrad, May F.,Hirz, Taghreed,El Hachem, Nehme,Khalaf, Ali,Hammoud, Soukaina,Fayyad-Kazan, Hussein,Eid, Assaad A.,Badran, Bassam,Merhi, Raghida Abou,Hachem, Ali,Hamade, Eva,Habib, A?da
, p. 66 - 73 (2015/02/19)
Cyclooxygenases (COXs) are important membrane-bound heme containing enzymes important in platelet activation and inflammation. COX-1 is constitutively expressed in most cells whereas COX-2 is an inducible isoform highly expressed in inflammatory condition
TPA-induced up-regulation of activator protein-1 can be inhibited or enhanced by analogs of the natural product curcumin
Weber, Waylon M.,Hunsaker, Lucy A.,Gonzales, Amanda M.,Heynekamp, Justin J.,Orlando, Robert A.,Deck, Lorraine M.,Vander Jagt, David L.
, p. 928 - 940 (2007/10/03)
The activator protein-1 (AP-1) family of transcription factors, including the most common member c-Jun-c-Fos, participates in regulation of expression of numerous genes involved in proliferation, apoptosis, and tumorigenesis in response to a wide array of stimuli including pro-inflammatory cytokines, growth factors, stress, and tumor promoters. A number of plant polyphenols including curcumin, a yellow compound in the spice turmeric, have been shown to inhibit the activation of AP-1. Curcumin is a polyphenolic dienone that is potentially reactive as a Michael acceptor and also is a strong anti-oxidant. Multiple activities reported for curcumin, including inhibition of the stress-induced activation of AP-1, have been suggested to involve the anti-oxidant properties of curcumin. In the present study, a library of analogs of curcumin was screened for activity against the TPA-induced activation of AP-1 using the Panomics AP-1 Reporter 293 stable cell line which is designed for screening potential inhibitors. Numerous analogs were identified that were more active than curcumin, including analogs that were not anti-oxidants and analogs that were not Michael acceptors. Clearly, anti-oxidant activity or reactivity as a Michael acceptor is not an essential feature of active compounds. In addition, a number of analogs were identified that enhanced the TPA-induced activation of AP-1. The results from screening were confirmed using BV-2 microglial cells where curcumin and analogs were shown to inhibit LPS-induced COX-2 expression; analogs identified as more potent than curcumin in the screening assay were also more potent than curcumin in preventing COX-2 expression.
