Journal
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
Volume 94, Issue -, Pages 436-446Publisher
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2014.11.054
Keywords
Curcumin; Acute lung injury; Drug design; Chemical stability; Cytokines
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Funding
- National Natural Science Foundation of China [21202124, 21272179, 21472142]
- Project of Zhejiang Provincial Key Constructive Subject (Traditional Chinese Medicine) [2012-XK-A28]
- Qianjiang Talent Project of Zhejiang Province [2013R10020]
- Zhejiang Medical & Health Science and Technology Project [2013KYB168]
- Zhejiang Natural Science Funding [LQ12H30002]
- SRF for ROCS, SEM
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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-alpha 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. (C) 2015 Published by Elsevier Masson SAS.
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