title: Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.
abstract: Bisphosphonates (BPs) are now the most widely used drugs for diseases associated with increased bone resorption, such as osteoporosis, and tumor bone diseases. A significant drawback of the BPs is their poor oral absorption that is enhanced by the presence of bile acid substituents in the bisphosphonate framework, with no toxic effects. A straightforward synthesis of bile acid-containing hydroxy-bisphosphonates and a full characterization of these pharmaceutically important molecules, including an evaluation of affinity and the mechanism of binding to hydroxyapatite, is presented. The biological activity of bile acid-containing bisphosphonate salts was determined using the neutral-red assay on the L929 cell line and primary cultures of osteoclasts. The bioactivity of the new compounds was found superior than bisphosphonates of established activity.
authors.affiliation: Dipartimento di Chimica and SOF-CNR sezione di Ferrara, Università di Ferrara, Via Borsari 46, 44121 Ferrara, Italy. olga.bortolini@unife.it
authors.forename: Olga
authors.initials: O
authors.lastname: Bortolini
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Fantin
authors.forename: Marco
authors.initials: M
authors.lastname: Fogagnolo
authors.forename: Stefano
authors.initials: S
authors.lastname: Rossetti
authors.forename: Loredana
authors.initials: L
authors.lastname: Maiuolo
authors.forename: Gemma
authors.initials: G
authors.lastname: Di Pompo
authors.forename: Sofia
authors.initials: S
authors.lastname: Avnet
authors.forename: Donatella
authors.initials: D
authors.lastname: Granchi
mesh_terms: D000042:Absorption; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001647:Bile Acids and Salts / Q000737:chemistry*; D002460:Cell Line; D060326:Chemistry Techniques, Synthetic; D004164:Diphosphonates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017886:Durapatite / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D006878:Hydroxides / Q000737:chemistry*; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects
chemical_list: D001647:Bile Acids and Salts; D004164:Diphosphonates; D006878:Hydroxides; C031356:hydroxide ion; D017886:Durapatite