목적: Prostaglandin(PG)s have a short lifetime in vivo because they are metabolized rapidly by oxidation by the 15-hydroxyPG dehydrogenase (15-PGDH). This enzyme is ubiquitous in mammalian tissue and is responsible for the biological inactivation of prostaglandins. Therefore, inhibitors of 15-PGDH will be valuable for the therapeutic management of diseases requiring elevated prostaglandin levels. 방법:Novel thiazolidinedione analogues as 15-PGDH inhibitors were synthesized. Compounds 2, 3, and 4 exhibited IC50 of 25, 8, and 19 nM, respectively. To evaluate the selectivity of 2 for inhibition of 15-PGDH in IL-1β-stimulated A549 cells, 2 and 2a were added at various concentrations and incubated and the level of PGE2 was analyzed by ELISA. To assess the influence of 15-PGDH inhibitor on cochlear blood flow (CBF), Compound 2 was applied intravenously to guinea pigs. To study wound healing, scratch wound analysis was performed in confluent monolayers of HaCaT cells. To evaluate the effect of 15-PGDH inhibitors on the regulation of COX-1/2, MRP4, and PGT in cells, real time PCR was studied against COX-1/2, MRP4, and PGT in A549 cell lines. 결과:ELISA showed that the levels of PGE2 were significantly increased. CBF began to increase after 30 min, reaching plateaus of 22% 40 min after the intravenous application of 10 μg and 65% 50 min after the application of 20 μg. The plateau levels were maintained for at least 10 min. Cells exposed to compound 4 showed significantly improved wound healing after 48 h with respect to a control. PCR data showed that 2 and 3 inhibited COX-1 expression; they induced hPGT expression and had no significant effect on COX-2 or MRP4 expression. 결론:15-PGDH inhibitors may be useful to treat diseases such as Burerger’s diseases and diabetic neuropathy, and wounds, which require elevated prostaglandin levels. It can also be applied to sudden sensorineural hearing loss, tinnitus and tympanic membrane regeneration.