pmid: 31752552,   nlmid 101150203,  doi:10.1080/14756366.2019.1693703

Discovery of talmapimod analogues as polypharmacological anti-inflammatory agents.


Liu, Wandong Hou, Caiyun Li, Jiaming Ma, Xiaodong Zhang, Yanchun Hu, Mengqi Huang, Yuanzheng

Vol. 35, Issue 35, Dec.2020

Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem),  ISSN 1475-6374

Abstract

Twenty novel talmapimod analogues were designed, synthesised and evaluated for the in vivo anti-inflammatory activities. Among them, compound , the most potent one, was selected for exploring the mechanisms underlying its anti-inflammatory efficacy. In RAW264.7 cells, it effectively suppressed lipopolysaccharides-induced (LPS-induced) expressions of iNOS and COX-2. As illustrated by the western blot analysis, downregulated both the NF-?B signalling and p38 MAPK phosphorylation. Further enzymatic assay identified as a potent inhibitor against both p38? MAPK (IC=1.95?µM) and COX-2 (IC=0.036?µM). By virtue of the concomitant inhibition of p38? MAPK, its upstream effector, and COX-2, along with its capability to downregulate NF-?B and MAPK-signalling pathways, , a polypharmacological anti-inflammatory agent, deserves further development as a novel anti-inflammatory drug.


MESH Headings


Article Keywords

COXs | Polypharmacological agent | anti-inflammation | p38? MAPK | talmapimod analogues |


Chemical

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