2. Academic Validation
  3. Bisphosphonate prodrugs: synthesis and biological evaluation in HuH7 hepatocarcinoma cells

Bisphosphonate prodrugs: synthesis and biological evaluation in HuH7 hepatocarcinoma cells

  • Eur J Med Chem. 2014 Apr 22:77:56-64. doi: 10.1016/j.ejmech.2014.02.054.
Maelle Monteil 1,  Evelyne Migianu-Griffoni 1,  Odile Sainte-Catherine 1,  Mélanie Di Benedetto 1,  Marc Lecouvey 2
Affiliations

Affiliations

  • 1 Université Paris 13, Sorbonne Paris Cité, Laboratoire de Chimie, Structure, Propriétés de Biomatériaux et d'Agents Thérapeutiques (CSPBAT), CNRS UMR 7244, 74, Rue Marcel Cachin, F-93017 Bobigny, France.
  • 2 Université Paris 13, Sorbonne Paris Cité, Laboratoire de Chimie, Structure, Propriétés de Biomatériaux et d'Agents Thérapeutiques (CSPBAT), CNRS UMR 7244, 74, Rue Marcel Cachin, F-93017 Bobigny, France. Electronic address: marc.lecouvey@univ-paris13.fr.
PMID: 24607589 DOI: 10.1016/j.ejmech.2014.02.054
Abstract

We investigated the biological effects of new synthesized bisphosphonates (BPs) on HuH7 hepatocarcinoma cells. BPs containing p-bromophenyl (R1 = p-Br, Ph, 2) in their side chain were the more potent to inhibit HuH7 cell viability. In addition, phenyl diesterified analogues (R2 = R3 = Ph, 2a) were more potent than methyl (R2 = R3 = Me, 2b) or non-esterified BPs (2) inducing more necrosis suggesting that they better entered into cells. Phosphodiesterase inhibitor (IBMX) reversed the effect of the esterified BPs and not that of non-esterified ones suggesting role of cell phosphodiesterases to release active BPs. BP analogues inhibited HuH7 cell migration but esterified ones had no effect on invasion due to the hiding of phosphonic groups. All together, these results indicated the therapeutic interest of these new BP prodrugs.

Keywords

Bisphosphonates; Hepatocarcinoma; Phosphodiesterase inhibitor (IBMX); Prodrugs.

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