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Eur J Med Chem. 2015 Apr 13;94:436-46. doi: 10.1016/j.ejmech.2014.11.054. Epub 2015 Jan 7.

Design, synthesis and biological activity of novel asymmetric C66 analogs as anti-inflammatory agents for the treatment of acute lung injury.

Author information

1
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China.
2
Department of Pediatrics, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China.
3
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China. Electronic address: zjm@wzmc.edu.cn.
4
Chemical Biology Research Center at School of Pharmaceutical Sciences, Wenzhou Medical University, 1210 University Town, Wenzhou, Zhejiang 325035, China; Wenzhou Undersun Biotechnology Co., Ltd., Wenzhou, Zhejiang, China. Electronic address: lzgcnu@163.com.

Abstract

Acute lung injury (ALI) is a leading cause of morbidity and mortality in critically-ill patients. Previously, we reported that a symmetric mono-carbonyl analog of curcumin, (C66), exhibits enhanced stability and was found to have efficacy and be involved in potential cytokines inhibition. In the present study, a series of novel asymmetric C66 analogs were designed and synthesized. A majority of them effectively inhibited the LPS-induced expression of TNF-α and IL-6. Significantly, compound 4b2 was found to effectively reduce LPS-induced pulmonary inflammation, as reflected by reductions in concentration of total protein, inflammatory cell count as well as the lung W/D ratio in bronchoalveolar lavage (BAL) fluid. Furthermore, in vivo administration of 4b2 resulted in remarkable improvement in histopathological changes of lung in rats.

KEYWORDS:

Acute lung injury; Chemical stability; Curcumin; Cytokines; Drug design

PMID:
25828826
DOI:
10.1016/j.ejmech.2014.11.054
[Indexed for MEDLINE]

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