title: Vascular disrupting activity of tubulin-binding 1,5-diaryl-1H-imidazoles.
abstract: Highly cytotoxic 1,5-diaryl-1H-imidazoles were studied to clarify the relationship between cytotoxicity and activity as vascular disrupting agents (VDA). All the compounds disorganized the tubulin cytoskeleton, affected endothelial cell morphology and capillary formation in vitro, and caused vessel shutdown and tumor necrosis in vivo, thus confirming their vascular disrupting properties. Nonetheless, the substitution patterns on the imidazole ring, responsible for greater interaction energy with tubulin and higher cytotoxicity, were not associated to greater vascular disrupting activity.
authors: Department of Oncology, Mario Negri Institute for Pharmacological Research, via Gavazzeni 11, 24125 Bergamo, Italy.
authors: Katiuscia
authors: K
authors: Bonezzi
authors: Giulia
authors: G
authors: Taraboletti
authors: Patrizia
authors: P
authors: Borsotti
authors: Fabio
authors: F
authors: Bellina
authors: Renzo
authors: R
authors: Rossi
authors: Raffaella
authors: R
authors: Giavazzi
mesh_terms: D000818:Animals; D001665:Binding Sites; D001808:Blood Vessels / Q000187:drug effects* / Q000378:metabolism; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D006851:Hydrochloric Acid / Q000737:chemistry; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D007536:Isomerism; D051379:Mice; D009369:Neoplasms / Q000098:blood supply; D014404:Tubulin / Q000378:metabolism*
chemical_list: D007093:Imidazoles; D014404:Tubulin; D006851:Hydrochloric Acid