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

Olga Bortolini, Giancarlo Fantin, Marco Fogagnolo, Stefano Rossetti, Loredana Maiuolo, Gemma Di Pompo, Sofia Avnet, Donatella Granchi

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)221-229
Number of pages9
JournalEuropean Journal of Medicinal Chemistry
Volume52
DOIs
Publication statusPublished - Jun 2012

Fingerprint

Diphosphonates
Bioactivity
Bile Acids and Salts
Hydroxyl Radical
Bone
Neutral Red
Poisons
Bone Diseases
Osteoclasts
Durapatite
Bone Resorption
Cell culture
Osteoporosis
Tumors
Assays
Salts
Cells
Cell Line
Molecules
Pharmaceutical Preparations

Keywords

  • Bile acids
  • Biological activity
  • Hydroxy-bisphosphonates
  • Hydroxyapatite affinity

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Synthesis, characterization and biological activity of hydroxyl- bisphosphonic analogs of bile acids. / Bortolini, Olga; Fantin, Giancarlo; Fogagnolo, Marco; Rossetti, Stefano; Maiuolo, Loredana; Di Pompo, Gemma; Avnet, Sofia; Granchi, Donatella.

In: European Journal of Medicinal Chemistry, Vol. 52, 06.2012, p. 221-229.

Research output: Contribution to journalArticle

Bortolini, Olga ; Fantin, Giancarlo ; Fogagnolo, Marco ; Rossetti, Stefano ; Maiuolo, Loredana ; Di Pompo, Gemma ; Avnet, Sofia ; Granchi, Donatella. / Synthesis, characterization and biological activity of hydroxyl- bisphosphonic analogs of bile acids. In: European Journal of Medicinal Chemistry. 2012 ; Vol. 52. pp. 221-229.
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