کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1359048 | 981380 | 2010 | 9 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Design, synthesis, and biological evaluation of prenylated chalcones as 5-LOX inhibitors Design, synthesis, and biological evaluation of prenylated chalcones as 5-LOX inhibitors](/preview/png/1359048.png)
Ten novel mono- and di-O-prenylated chalcone derivatives were designed on the basis of a homology derived molecular model of 5-lipoxygenase (5-LOX). The compounds were docked into 5-LOX active site and the binding characteristics were quantified using LUDI. To verify our theoretical assumption, the molecules were synthesized and tested for their 5-LOX inhibitory activities. The synthesis was carried out by Claisen–Schmidt condensation reaction of mono- and di-O-prenylated acetophenones with appropriate aldehydes. 5-LOX in vitro inhibition assay showed higher potency of di-O-prenylated chalcones than their mono-O-prenylated chalcone analogs. Compound 5e exhibited good inhibition with an IC50 at 4 μM. The overall trend for the binding energies calculated and LUDI score was in good qualitative agreement with the experimental data. Further, the compound 5e showed potent anti-proliferative effects (GI50 at 9 μM) on breast cancer cell line, MCF-7.
In this study, a series of 10 novel mono- and di-O-prenylated chalcone derivatives were designed, synthesized, and screened for their in vitro 5-LOX inhibition activity and anti-proliferative activity.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry - Volume 18, Issue 16, 15 August 2010, Pages 5807–5815