Synthesis, characterization and biological activity of hydroxyl-bisphosphonic analogs of bile acids.

Autor: Bortolini O; Dipartimento di Chimica and SOF-CNR sezione di Ferrara, Università di Ferrara, Via Borsari 46, 44121 Ferrara, Italy. olga.bortolini@unife.it, Fantin G, Fogagnolo M, Rossetti S, Maiuolo L, Di Pompo G, Avnet S, Granchi D
Jazyk: angličtina
Zdroj: European journal of medicinal chemistry [Eur J Med Chem] 2012 Jun; Vol. 52, pp. 221-9. Date of Electronic Publication: 2012 Mar 19.
DOI: 10.1016/j.ejmech.2012.03.020
Abstrakt: 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.
(Copyright © 2012 Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE
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