A Novel Approach for Bisphosphonates: Ionic Liquids and Organic Salts from Zoledronic Acid

ChemMedChem. 2019 Oct 17;14(20):1767-1770. doi: 10.1002/cmdc.201900397. Epub 2019 Oct 11.

Abstract

Novel ionic liquids and organic salts based on mono- or dianionic zoledronate and protonated superbases, choline and n-alkylmethylimidazolium cations, were prepared and characterized by spectroscopic and thermal analyses. Most of the prepared salts display amorphous structures and very high solubility in water and saline solutions, especially the dianionic salts. Among the zoledronate-based ionic compounds, those containing choline [Ch] and methoxyethylmethylimidazolium [C3 OMIM] cations appear to have significant cytotoxicity against human osteosarcoma cells (MG63) and low toxicity toward healthy skin fibroblast cells. Because osteosarcoma is a bone pathology characterized by an increase in bone turnover rate, the results presented herein may be a promising starting point for the development of new ionic pharmaceutical drugs against osteosarcoma.

Keywords: API-OSIL; bioavailability; cytotoxicity; ionic liquids; zoledronic acid.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Diphosphonates / chemistry
  • Diphosphonates / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Fibroblasts / drug effects*
  • Humans
  • Ionic Liquids / chemistry
  • Ionic Liquids / pharmacology*
  • Molecular Structure
  • Salts / chemistry
  • Salts / pharmacology
  • Structure-Activity Relationship
  • Zoledronic Acid / chemistry
  • Zoledronic Acid / pharmacology*

Substances

  • Antineoplastic Agents
  • Diphosphonates
  • Ionic Liquids
  • Salts
  • Zoledronic Acid