Design, synthesis, and biological evaluation of prenylated chalcones as 5-LOX inhibitors.

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Reddy NP, Aparoy P, Reddy TC, Achari C, Sridhar PR, Reddanna P

Design, synthesis, and biological evaluation of prenylated chalcones as 5-LOX inhibitors.

Bioorg Med Chem. 2010 Aug 15;18(16):5807-15. doi: 10.1016/j.bmc.2010.06.107. Epub 2010 Jul 6.

PubMed ID

20667741 [ View in PubMed

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Abstract

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 IC(50) at 4 microM. 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 (GI(50) at 9 microM) on breast cancer cell line, MCF-7.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Masoprocol	Arachidonate 5-lipoxygenase	IC 50 (nM)	1500	N/A	N/A	Details