title: Bisphosphonate prodrugs: synthesis and biological evaluation in HuH7 hepatocarcinoma cells.
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.
authors.affiliation: 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.
authors.forename: Maelle
authors.initials: M
authors.lastname: Monteil
authors.affiliation: 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.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Migianu-Griffoni
authors.affiliation: 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.
authors.forename: Odile
authors.initials: O
authors.lastname: Sainte-Catherine
authors.affiliation: 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.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Di Benedetto
authors.affiliation: 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.
authors.forename: Marc
authors.initials: M
authors.lastname: Lecouvey
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004164:Diphosphonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; D011355:Prodrugs
keywords: Bisphosphonates; Hepatocarcinoma; Phosphodiesterase inhibitor (IBMX); Prodrugs