title: Novel 1,4-benzoxazine and 1,4-benzodioxine inhibitors of angiogenesis.
abstract: Esters of 1,4-benzoxazine and 1,4-benzodioxine compounds 1 and 10, which combine thrombin inhibitory and GPIIb/IIIa antagonistic activity in one molecule are shown to inhibit endothelial cell migration and tube formation in vitro and angiogenesis in the chicken chorioallantoic membrane (CAM) assay. The corresponding carboxylic acids 1 (R(2) = H) and 11 were devoid of anti-angiogenic activity, most probably due to their insufficient entry into the cell. Although thrombin inhibition remains the most probable explanation for their inhibition of angiogenesis, VEGFR2 kinase assay suggest that other targets such as VEGFR2 might be involved.
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, SI - 1000 Ljubljana, Slovenia.
authors.forename: Miloš
authors.initials: M
authors.lastname: Ilić
authors.forename: Janez
authors.initials: J
authors.lastname: Ilaš
authors.forename: Petra
authors.initials: P
authors.lastname: Dunkel
authors.forename: Péter
authors.initials: P
authors.lastname: Mátyus
authors.forename: Andrej
authors.initials: A
authors.lastname: Boháč
authors.forename: Sandra
authors.initials: S
authors.lastname: Liekens
authors.forename: Danijel
authors.initials: D
authors.lastname: Kikelj
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D048588:Benzoxazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002417:Cattle; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000187:drug effects; D004146:Dioxanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D042783:Endothelial Cells / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D015394:Molecular Structure; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D048588:Benzoxazines; D004146:Dioxanes; D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013917:Thrombin