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

被引：6

作者：

Dong, Lili ^{[1
,2
]}

Zheng, Suqing ^{[1
]}

Zhang, Yali ^{[1
]}

Jiang, Xin ^{[3
]}

Wu, Jianzhang ^{[1
]}

Zhang, Xiaoqin ^{[4
]}

Shan, Xiaoou ^{[2
]}

Liang, Dandan ^{[1
]}

Ying, Shilong ^{[1
]}

Feng, Jianpeng ^{[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, Affiliated Hosp 2, Wenzhou 325035, Zhejiang, Peoples R China

[3] Zhejiang Univ Sch Med, Childrens Hosp, Hangzhou 310003, Zhejiang, Peoples R China

[4] Wenzhou Med Univ, Sch Lab Med & Life Sci, Wenzhou 325035, Zhejiang, Peoples R China

来源：

MEDCHEMCOMM | 2015年 / 6卷 / 08期

关键词：

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

D O I：

10.1039/c5md00113g

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：

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.

引用

页码：1544 / 1553

页数：10

共 35 条

[1]

Aggarwal BB, 2007, ADV EXP MED BIOL, V595, P1

[2] Bioavailability of curcumin: Problems and promises [J].

Anand, Preetha ;

Kunnumakkara, Ajaikumar B. ;

Newman, Robert A. ;

Aggarwal, Bharat B. .

MOLECULAR PHARMACEUTICS, 2007, 4 (06) :807-818

[3] Curcumin alone and in combination with augmentin protects against pulmonary inflammation and acute lung injury generated during Klebsiella pneumoniae B5055-induced lung infection in BALB/c mice [J].

Bansal, Shruti ;

Chhibber, Sanjay .

JOURNAL OF MEDICAL MICROBIOLOGY, 2010, 59 (04) :429-437

[4] Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome [J].

Bhatia, M ;

Moochhala, S .

JOURNAL OF PATHOLOGY, 2004, 202 (02) :145-156

[5]

Chattopadhyay I, 2004, CURR SCI INDIA, V87, P44

[6]

Cheng AL, 2001, ANTICANCER RES, V21, P2895

[7] CurcuminuFrom Molecule to Biological Function [J].

Esatbeyoglu, Tuba ;

Huebbe, Patricia ;

Ernst, Insa M. A. ;

Chin, Dawn ;

Wagner, Anika E. ;

Rimbach, Gerald .

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 2012, 51 (22) :5308-5332

[8]

Frutos-Vivar Fernando, 2004, Curr Opin Crit Care, V10, P1, DOI 10.1097/00075198-200402000-00001

[9] Cytokine-mediated inflammation in acute lung injury [J].

Goodman, RB ;

Pugin, J ;

Lee, JS ;

Matthay, MA .

CYTOKINE & GROWTH FACTOR REVIEWS, 2003, 14 (06) :523-535

[10] Emergent mechanistic diversity of enzyme-catalysed β-diketone cleavage [J].

Grogan, G .

BIOCHEMICAL JOURNAL, 2005, 388 :721-730

← 1 2 3 4 →