Synthesis and Anti-Inflammatory Evaluation of Novel C66 Analogs for the Treatment of LPS-Induced Acute Lung Injury

被引：11

作者：

Feng, Jianpeng ^{[1
]}

Xiao, Bing ^{[1
]}

Chen, Wenbo ^{[1
]}

Ding, Ting ^{[2
]}

Chen, Lingfeng ^{[1
]}

Yu, Pengtian ^{[1
]}

Xu, Fengli ^{[3
]}

Zhang, Huajie ^{[1
]}

Liu, Zhiguo ^{[1
]}

Liang, Guang ^{[1
]}

机构：

[1] Wenzhou Med Univ, Sch Pharmaceut Sci, Chem Biol Res Ctr, Wenzhou 325035, Zhejiang, Peoples R China

[2] Wenzhou Med Univ, Lishui Peoples Hosp, Translat Med Res Ctr, Lishui 323000, Zhejiang, Peoples R China

[3] Wenzhou Med Univ, Affiliated Hosp 2, Dept Paediat, Wenzhou 325000, Zhejiang, Peoples R China

来源：

CHEMICAL BIOLOGY & DRUG DESIGN | 2015年 / 86卷 / 04期

关键词：

acute lung injury; C66; chemical stability; drug design; synthesis; NF-KAPPA-B; MONO-CARBONYL ANALOGS; MONOCARBONYL ANALOGS; DIABETIC-RATS; CURCUMIN; ANTIOXIDANT; INHIBITION; DISEASES; MICE;

D O I：

10.1111/cbdd.12548

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We previously reported a symmetric monocarbonyl analog of curcumin (MACs), C66, which demonstrated potential anti-inflammatory activity and low toxicity. In continuation of our ongoing research, we designed and synthesized 34 asymmetric MACs based on C66 as a lead molecule. A majority of the C66 analogs effectively inhibited LPS induction of TNF- and IL-6 expression. Additionally, a preliminary SAR was conducted. Furthermore, active compounds 4a11 and 4a16 were found to effectively reduce theW/D ratio in the lungs and the protein concentration in the bronchoalveolar lavage fluid (BALF). Meanwhile, a histopathological examination indicated that these two analogs significantly attenuate tissue injury in the lungs with LPS-induced ALI rats. 4a11 and 4a16 also inhibited mRNA expression of several inflammatory cytokines, including TNF-, IL-6, IL-1, COX-2, ICAM-1 and VCAM-1, in the Beas-2B cellsafter LPS challenge. Altogether, the data exhibit a series of new C66 analogs as promising anti-inflammatory agents for the treatment of LPS-induced ALI.

引用

页码：753 / 763

页数：11

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