Design, synthesis, and evaluation of semi-conservative mono-carbonyl analogs of curcumin as anti-inflammatory agents against lipopolysaccharide-induced acute lung injury

作者：Dong, Lili; Zheng, Suqing; Zhang, Yali; Jiang, Xin; Wu, Jianzhang; Zhang, Xiaoqin; Shan, Xiaoou; Liang, Dandan; Ying, Shilong; Feng, Jianpeng^*; Liang, Guang

来源：Medchemcomm, 2015, 6(8): 1544-1553.

DOI：10.1039/c5md00113g

• RESPIRATORY-DISTRESS-SYNDROME
• INFLAMMATION
• PROTECTS
• PATHOPHYSIOLOGY
• REDUCTION
• RATS
• MICE

Acute lung injury (ALI), one of a few severe diseases with high mortality, cannot be tackled by any effective therapies so far. Pro-inflammatory cytokines play an essential role in the pathogenesis of ALI. In order to discover novel anti-inflammatory agents against ALI, 37 semi-conservative mono-carbonyl analogs of curcumin (ScMACs) were designed, synthesized and screened for anti-inflammatory activities. The majority of these compounds exhibited remarkable inhibition of the expression of inflammatory cytokines in LPS-stimulated macrophages. Among them, compounds 6, 7, 10 and 18, efficiently inhibited the secretion of TNF-alpha and IL-6 in a dose-dependent manner. The most potent analog, compound 6, prevented the LPS-induced elevation of inflammatory gene expression, and alleviated the lung inflammatory cell infiltration and histopathological changes in vivo. Therefore, compound 6 is a potential lead for developing new anti-inflammatory candidate drugs against LPS-induced ALI.

• 出版日期2015
• 单位浙江大学; 温州医科大学