期刊
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
卷 46, 期 7, 页码 2722-2735出版社
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.ejmech.2011.03.060
关键词
Curcumin analogues; Lipoxygenase; Aldose reductase; Carrageenin; Anti-inflammatory activity; Anti-proliferative activity
资金
- Bodossakis Foundation
- Greek State Scholarship Foundation (IKY)
- Research Committee of Aristotle University of Thessaloniki
A series of novel curcumin analogues has been designed, synthesized and tested in vitro/in vivo as potential multi-target agents. Their anti-proliferative and anti-inflammatory activities were studied. Compounds 1b and 2b were stronger inhibitors of soybean lipoxygenase (LOX) than curcumin. Analogue 1b was also the most potent aldose reductase (ALR2) inhibitor. Two compounds, (1a and 1f) exhibited in vivo anti-inflammatory activity comparable to that of indomethacin, whereas derivative 1i exhibited even higher activity. The derivatives were also tested for their anti-proliferative activity using three different human cancer cell lines. Compounds 1a, 1b, 1d and 2b exhibited significant growth inhibitory activity as compared to curcumin, against all three cancer cell lines. Lipophilicity was determined as R-M values using RPTLC and theoretically. The results are discussed in terms of the structural characteristics of the compounds. Docking simulations were performed on LOX and ALR2 inhibitor 1b and curcumin. Compound 1b is well fitted in the active site of ALR2, binding to the ALR2 enzyme in a similar way to curcumin. Allosteric interactions may govern the LOX-inhibitor binding. (C) 2011 Elsevier Masson SAS. All rights reserved.
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