title: Structure-activity relationship studies of flavonoids as potent inhibitors of human platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2.
abstract: Human lipoxygenase (hLO) isozymes have been implicated in a number of disease states and have attracted much attention with respect to their inhibition. One class of inhibitors, the flavonoids, have been shown to be potent lipoxygenase inhibitors but their study has been restricted to those compounds found in nature, which have limited structural variability. We have therefore carried out a comprehensive study to determine the structural requirements for flavonoid potency and selectivity against platelet 12-hLO, reticulocyte 15-hLO-1, and prostate epithelial 15-hLO-2. We conclude from this study that catechols are essential for high potency, that isoflavones and isoflavonones tend to select against 12-hLO, that isoflavons tend to select against 15-hLO-1, but few flavonoids target 15-hLO-2.
authors.affiliation: Laboratorio de Investigación Científica Emory Black, Escuela de Medicina, Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Casilla 442, Correo 2 Santiago, Chile.
authors.forename: Yesseny
authors.initials: Y
authors.lastname: Vasquez-Martinez
authors.forename: Rachana V
authors.initials: RV
authors.lastname: Ohri
authors.forename: Victor
authors.initials: V
authors.lastname: Kenyon
authors.forename: Theodore R
authors.initials: TR
authors.lastname: Holman
authors.forename: Silvia
authors.initials: S
authors.lastname: Sepúlveda-Boza
mesh_terms: D001092:Arachidonate 12-Lipoxygenase / Q000097:blood / Q000302:isolation & purification; D001093:Arachidonate 15-Lipoxygenase / Q000302:isolation & purification; D004353:Drug Evaluation, Preclinical; D004847:Epithelial Cells / Q000201:enzymology*; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000302:isolation & purification; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D011467:Prostate / Q000201:enzymology; D012156:Reticulocytes / Q000201:enzymology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D005419:Flavonoids; D007527:Isoenzymes; D016859:Lipoxygenase Inhibitors; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase