Effects of flavonoids on the release of reactive oxygen species by stimulated human neutrophils: Multivariate analysis of structure-activity relationships (SAR)

摘要: In the present study we measured inhibition by 34 compounds, either flavonoids or related substances, of release reactive oxygen species human neutrophils after stimulation three agents: bacterial peptide N-fMetLeuPhe (FMLP), protein kinase C activator phorbol myristate acetate (PMA) opsonized zymosan (OZ), using two chemiluminescent probes, lucigenin luminol in presence absence horseradish peroxidase (HRP). The data matrix (34 x 7) was submitted to multivariate analysis: first, a correspondence factorial analysis uncover levels correlation among biochemical parameters and specificity action test-compounds second, minimum spanning tree that classified chemical structures into network describing both amplitude chemiluminescence response. major conclusions analyses were: (a) opposition between poly-morphonuclear leukocytes (PMNs) stimulated FMLP PMNs PMA OZ implying that, for molecules under study, there fundamental difference manner which this occurred and, conversely, nature stimulatory these activators. Molecules lacking hydroxyl groups on ring B, i.e. chrysin, chalcone, flavone galangin, glycosylated position 7, hesperidin naringin B mono-hydroxylated were, most part, at origin dichotomy might interfere with membrane receptor; (b) marked HRP can be explained differential catechins compared flavonol derivatives; (c) similarity biological profile non-flavonoids such as chalcone phloretin low mean-activity chrysin galangin non-flavonoid curcumin highly active flavonoid isorhamnetin; (d) reaffirmation importance A (C5,7) (C3',4') dihydroxylation, (C3) hydroxylation, but also methoxy group engendering high potency. This potency is generally decreased C2-C3 saturation glycosylation. identified provide valuable information selection simpler (e.g. metabolites accounting orally administered flavonoids) further structure-activity relationship (SAR) studies could lead design novel drugs prodrugs.