Low toxicity and unprecedented anti-osteoclast activity of a simple sulfur-containing gem-bisphosphonate: A comparative study

Donatella Granchi, Alessandro Scarso, Giulio Bianchini, Andrea Chiminazzo, Alberto Minto, Paolo Sgarbossa, Rino A. Michelin, Gemma Di Pompo, Sofia Avnet, Giorgio Strukul

Research output: Contribution to journalArticlepeer-review

Abstract

Bisphosphonates (BPs) are key drugs for the treatment of bone resorption diseases like osteoporosis, Paget's disease and some forms of tumors. Recent findings underlined the importance of lipophilic N-containing BPs to ensure high biological activity. Herein we present some unprecedented results concerning the low toxicity and good anti-osteoclast activity of low molecular weight hydrophilic S-containing BPs. A series of S and N-containing BPs bearing aromatic and aliphatic substitution were prepared through Michael addition reaction between vinylidenebisphosphonate tetraethyl ester and the proper nucleophile under basic catalysis. S-containing BPs showed a generally low toxicity, determined with the neutral-red assay using the L929 cell line, and, in particular for an aliphatic one, a good biological activity assessed on primary cultures of human osteoclasts.

Original languageEnglish
Pages (from-to)448-455
Number of pages8
JournalEuropean Journal of Medicinal Chemistry
Volume65
DOIs
Publication statusPublished - 2013

Keywords

  • Apoptosis
  • Bisphosphonates
  • Cytotoxicity
  • Osteoclast
  • S-containing drugs

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

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