2-Substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole, a key structural moiety exiting in many bioactive molecules, has been shown to have excellent selective activity on COX-2. In the present study, the anti-inflammatory activity and the underlying molecular mechanism of 2-substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole on skin inflammation were assessed by 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mice. Most of the compounds showed anti-inflammatory activity on TPA-induced skin inflammation. The anti-inflammatory activity of compound 4 showed higher anti-inflammatory activity than celecoxib (3.2-fold). Compound 4 pretreatment resulted in markedly suppression of TPA-induced IL-1β, IL-6, TNF-α, and COX-2, respectively. Furthermore, the mechanical study indicated that the anti-inflammatory activity of compound 4 was associated with its ability to inhibit activation of factor kappa-κB (NF-κB) by blocking IκB kinase (IKK) activities. Accordingly, compound 4 could be used as a potential anti-inflammatory agent for skin inflammation.

中文翻译：

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2-取代-1,4,5,6-四氢环戊[b]吡咯对TPA诱导的小鼠皮肤炎症的抗炎作用

2-取代的1,4,5,6-四氢环戊[b]吡咯是许多生物活性分子中存在的关键结构部分，已显示对COX-2具有出色的选择性活性。在本研究中，通过12-O-十四烷酰佛波醇13-乙酸酯（TPA）评估了2-取代的1,4,5,6-四氢环戊[b]吡咯对皮肤炎症的抗炎活性及其潜在分子机制。 ）诱发小鼠皮肤发炎。大多数化合物对TPA引起的皮肤炎症显示出抗炎活性。化合物4的抗炎活性显示出比塞来昔布更高的抗炎活性（3.2倍）。化合物4预处理分别显着抑制TPA诱导的IL-1β，IL-6，TNF-α和COX-2。此外，力学研究表明，化合物4的抗炎活性与其通过阻断IκB激酶（IKK）活性抑制因子kappa-κB（NF-κB）活化的能力有关。因此，化合物4可用作皮肤炎症的潜在抗炎剂。