Design,synthesis, and biological evaluation of prenylated chalcones as 5-LOX inhibitors |
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Authors: | Nimmanapalli P. Reddy Polamarasetty Aparoy T. Chandra Mohan Reddy Chandrani Achari P. Ramu Sridhar Pallu Reddanna |
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Affiliation: | 1. School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India;2. School of Chemistry, University of Hyderabad, Hyderabad 500 046, India |
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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 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. |
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