earticle

영어

PGE2 is a major product derived from arachidonic acid through the cyclooxigenase pathway, being implicated in pain and inflammatory responses. However, the effects of PGE2 are multiple and sometimes seem to be functionally opposing. For example, PGE2 has been also identified as an important mediator of gastric ulcer healing, bone formation, and dermal wound healing. 15-PGDH catalyzes NAD+ dependent oxidation of 15(S)-hydroxyl group of prostaglandins and
has been considered a key enzyme involved in biological inactivation of prostaglandins. Therefore, inhibitors of 15-PGDH will be valuable for the therapeutic management of diseases in which elevated PGE2 levels are needed. Structure-activity analysis of thiazolidinediones
indicated that the nature of the moiety linking through ether linkage to benzylidenethiazolidine-2,4-dione plays an important role in inhibitory potency. Base on the structures of thiazolidinediones analogues and inhibitory activity, various benzylidene thiazolidinedione derivatives with different substituents on phenyl ring were synthesized using a series of reaction and test for 15-PGDH inhibitory activity. The most potent inhibitor of this series of compounds is 5-(4-(2-(thiophen-2-
yl)ethoxy)benzylidene)thiazolidine-2,4-dione with a IC50 of 0.031 nM.