title: Effect of hydroxyl substitution of flavone on angiogenesis and free radical scavenging activities: a structure-activity relationship studies using computational tools.
abstract: Angiogenesis is a key process needed for the growth and survival of solid tumors. Anti-angiogenesis may arrest the tumor growth and keep check on cancer metastasis. Developing antiangiogenic agents have remained a significant hope in the mainstream of anticancer research. The free radical implications in the initiation of cancers are well established. In the present studies, simple flavone and flavones with hydroxyl substitution in 'A' and 'C' ring at 3, 5, 6, and 7 were studied for antiangiogenic activities using chorioallantoic membrane (CAM) model and kinetics of DPPH (2,2-diphenyl-1-picryl hydrazine) and superoxide anion radical (SOR) scavenging activities. The docking of selected flavones with specific angiogenic targets such as vascular endothelial growth factor (VEGF), hypoxia inducible factor (HIF-1alpha) and vascular endothelial growth factor receptor-2 (VEGFR2) from human origin was carried out to focus the possible underlying mechanism of anti-angiogenesis. The result of the present studies shows that the 3-hydroxy substitution of the flavone was found to be the most promising lead for antiangiogenic activity in CAM model. The same was true for DPPH reduction with greater velocity as compared to other hydroxyl substitutions. However the 7- and 6-hydroxy substitution were observed to be more favourable for SOR scavenging activities as compared to other hydroxyl substitutions. The docking experiments shows that the VEGFR2 seems to be a structurally compatible target for tight binding of the flavones especially with 3-hydroxy substitution (-9.78 kcal/mole) as compared to VEGF (-8.47 kcal/mole) and HIF-1alpha (-8.99 kcal/mole). The quantum chemical descriptors of the test flavones related to free radical scavenging and other biological activities were calculated using computational tools. The data is discussed in the light of structure-activity relationship.
authors.affiliation: School of Life Sciences, Swami Ramanand Teerth Marathwada University, Vishnupuri, Nanded 431 606 (MS), India. rngacche@rediffmail.com
authors.forename: Gacche
authors.initials: G
authors.lastname: Rajesh
authors.forename: Shegokar
authors.initials: S
authors.lastname: Harshala
authors.forename: Gond
authors.initials: G
authors.lastname: Dhananjay
authors.forename: Archana
authors.initials: A
authors.lastname: Jadhav
authors.forename: Ghole
authors.initials: G
authors.lastname: Vikram
mesh_terms: D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000187:drug effects*; D047309:Flavones / Q000737:chemistry / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D006900:Hydroxylation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000737:chemistry; D021281:Quantitative Structure-Activity Relationship; D042461:Vascular Endothelial Growth Factor A / Q000737:chemistry; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000737:chemistry
chemical_list: D020533:Angiogenesis Inhibitors; D047309:Flavones; D005419:Flavonoids; D016166:Free Radical Scavengers; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; C043562:flavone