1215268-38-4Relevant articles and documents
Discovery of 3-(4-bromophenyl)-6-nitrobenzo[1.3.2]dithiazolium ylide 1,1-dioxide as a novel dual cyclooxygenase/5-lipoxygenase inhibitor that also inhibits tumor necrosis factor-α production
Chen, Chien-Shu,Tan, Chen-Ming,Huang, Chiung-Hua,Chang, Ling-Chu,Wang, Jih-Pyang,Cheng, Fong-Chi,Chern, Ji-Wang
experimental part, p. 597 - 604 (2010/05/02)
In the present study we have discovered compound 1, a benzo[1.3.2]dithiazolium ylide-based compound, as a new prototype dual inhibitor of cyclooxygenase (COX) and 5-lipoxygenase (5-LOX). Compound 1 was initially discovered as a COX-2 inhibitor, resulting indirectly from the COX-2 structure-based virtual screening that identified compound 2 as a virtual hit. Compounds 1 and 2 inhibited COX-1 and COX-2 in mouse macrophages with IC50 in the range of 1.5-18.1 μM. Both compounds 1 and 2 were also found to be potent inhibitors of human 5-LOX (IC50 = 1.22 and 0.47 μM, respectively). Interestingly, compound 1 also had an inhibitory effect on tumor necrosis factor-α (TNF-α) production (IC50 = 0.44 μM), which was not observed with compound 2. Docking studies suggested the (S)-enantiomer of 1 as the biologically active isomer that binds to COX-2. Being a cytokine-suppressive dual COX/5-LOX inhibitor, compound 1 may represent a useful lead structure for the development of advantageous new anti-inflammatory agents.
