earticle

영어

Thiazolidinedione analogue, CT-8, has been reported to be a potent inhibitor of human 15-hydroxyprostaglandin dehydrogenase (15-PGDH). In continuing attempts to develop highly potent 15-PGDH inhibitors, a series of thiazolidinedione analogues with different substituents on phenyl rings were synthesized and tested. Of the compounds produced, those in the low nanomolar range were most effective. In particular, introduction of halogen atoms at the phenyl ring of CT-8 greatly improved its inhibitory efficacy. For structure-activity analysis, the effects of adding cyclohexyl with different chain lengths to the hydroxyl groups of 5-(3-substituted-4-hydroxybenzylidene)thiazolidine-2,4-dione were tested. Removal of the methylene group between the cyclohexyl ring and oxygen of 5-(3-substituted-4-(2-cyclohexylethoxy)benzylidene)thiazolidine-2, 4-dione decreased its inhibitory potency. It appears that two methylene groups between the cyclohexyl ring and oxygen of 5-(3-substituted- 4-hydroxybenzylidene)thiazolidine-2,4-dione are optimal for inhibitory activity. The most potent inhibitor of this series of compounds is compound 5, (5-(3-chloro-4-(2-cyclohexylethoxy)benzyl)thiazolidine-2,4-dione), with an IC50 of 0.008 μM.