Affiliation:
1. School of Chemistry & Chemical Engineering, Henan University of Science and Technology, Luoyang 471003, China
2. School of Nursing, Henan University of Science and Technology, Luoyang 471003, China
3. The State Key Laboratory of Medicinal Chemical Biology & College of Chemistry, Nankai University, Tianjin 300071, China
4. College of Pharmacy, Nankai University, Tianjin 300071, China
5. Accendatech Company, Ltd., Tianjin 300384, China
Abstract
Acute lung injury (ALI) is a respiratory failure disease associated with high mortality rates in patients. The primary pathological damage is attributed to the excessive release of pro-inflammatory mediators in pulmonary tissue. However, specific therapy for ALI has not been developed. In this study, a series of novel ferulic acid-parthenolide (FA-PTL) and ferulic acid-micheliolide (FA-MCL) hybrid derivatives were designed, synthesized, and evaluated for their anti-inflammatory activities in vitro. Compounds 2, 4, and 6 showed pronounced anti-inflammatory activity against LPS-induced expression of pro-inflammatory cytokines in vitro. Importantly, compound 6 displayed good water solubility, and treatment of mice with compound 6 (10 mg/kg) significantly prevented weight loss and ameliorated inflammatory cell infiltration and edema in lung tissue, as well as improving the alveolar structure. These results suggest that compound 6 (((1aR,7aS,8R,10aS,10bS,E)-8-((dimethylamino)methyl)-1a-methyl-9-oxo-1a,2,3,6,7,7a,8,9,10a,10b-decahydrooxireno[2′,3′:9,10]cyclodeca[1,2-b]furan-5-yl)methyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate 2-hydroxypropane-1,2,3-tricarboxylate) might be considered as a lead compound for further evaluation as a potential anti-ALI agent.
Funder
Scientific and Technological Project of Henan Province
X.D.
Cited by
1 articles.
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