title: Design, synthesis, and biological evaluation of prenylated chalcones as 5-LOX inhibitors.
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.
authors.affiliation: School of Life Sciences, University of Hyderabad, Hyderabad, India.
authors.forename: Nimmanapalli P
authors.initials: NP
authors.lastname: Reddy
authors.forename: Polamarasetty
authors.initials: P
authors.lastname: Aparoy
authors.forename: T Chandra Mohan
authors.initials: TC
authors.lastname: Reddy
authors.forename: Chandrani
authors.initials: C
authors.lastname: Achari
authors.forename: P Ramu
authors.initials: PR
authors.lastname: Sridhar
authors.forename: Pallu
authors.initials: P
authors.lastname: Reddanna
mesh_terms: D001094:Arachidonate 5-Lipoxygenase / Q000737:chemistry / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D047188:Chalcones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D013329:Structure-Activity Relationship
chemical_list: D047188:Chalcones; D016859:Lipoxygenase Inhibitors; D001094:Arachidonate 5-Lipoxygenase