Anti-inflammatory activity effect of 2-substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole on TPA-induced skin inflammation in mice.
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.
School of Chemical and Environmental Engineering, Wuyi University, Jiangmen 529020, China; International Healthycare Innovation Institute (Jiangmen), China. Electronic address: wyuchemxxt@126.com.
Xue-Tao
XT
Xu
School of Pharmacy & State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China.
Xue-Qing
XQ
Mou
The Second Department of Cardiology, Gansu Provincial Hospital, Lanzhou 730000, China.
Qin-Mei
QM
Xi
School of Pharmacy & State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China.
Wei-Ting
WT
Liu
School of Chemical and Environmental Engineering, Wuyi University, Jiangmen 529020, China.
Wen-Feng
WF
Liu
School of Chemical and Environmental Engineering, Wuyi University, Jiangmen 529020, China.
Zhao-Jun
ZJ
Sheng
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA.
Xi
X
Zheng
School of Chemical and Environmental Engineering, Wuyi University, Jiangmen 529020, China.
Kun
K
Zhang
Laboratory of Natural Medicinal Chemistry & Green Chemistry, School of Light Industry and Chemical Engineering, Guangdong University of Technology, Guangzhou 510006, China.
Zhi-Yun
ZY
Du
Laboratory of Natural Medicinal Chemistry & Green Chemistry, School of Light Industry and Chemical Engineering, Guangdong University of Technology, Guangzhou 510006, China.
Su-Qing
SQ
Zhao
School of Pharmacy & State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China. Electronic address: wangshh@lzu.edu.cn.
Shao-Hua
SH
Wang
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003517:Cyclopentanes; D003872:Dermatitis / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011758:Pyrroles; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
C568058:1,4,5,6-tetrahydrocyclopenta(b)pyrrole; D000893:Anti-Inflammatory Agents; D003517:Cyclopentanes; D016328:NF-kappa B; D011758:Pyrroles; D013755:Tetradecanoylphorbol Acetate
2-Substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole; Anti-inflammatory activity; Skin disease; TPA