title: New symmetrically esterified m-bromobenzyl non-aminobisphosphonates inhibited breast cancer growth and metastases.
abstract: BACKGROUND
  Although there was growing evidence in the potential use of Bisphosphonates (BPs) in cancer therapy, their strong osseous affinities that contrast their poor soft tissue uptake limited their use. Here, we developed a new strategy to overcome BPs hydrophilicity by masking the phosphonic acid through organic protecting groups and introducing hydrophobic functions in the side chain.
  
  
  RESULTS
  We synthesized non-nitrogen BPs (non N-BPs) containing bromobenzyl group (BP7033Br) in their side chain that were symmetrically esterified with hydrophobic 4-methoxphenyl (BP7033BrALK) and assessed their effects on breast cancer estrogen-responsive cells (T47D, MCF-7) as well as on non responsive ones (SKBR3, MDA-MB-231 and its highly metastatic derived D3H2LN subclone). BP7033Br ALK was more efficient in inhibiting tumor cell proliferation, migration and survival when compared to BP7033Br. Although both compounds inhibited tumor growth without side effects, only BP7033Br ALK abrogated tumor angiogenesis and D3H2LN cells-induced metastases formation.
  
  
  CONCLUSIONS
  Taken together these data suggest the potential therapeutic use of this new class of esterified Bisphosphonates (BPs) in the treatment of tumor progression and metastasis without toxic adverse effects.
authors.affiliation: Université Paris 13, CNRS FRE CSPBAT, Laboratoire de Chimie Structurale Biomoléculaire, Laboratoire de pharmacologie, Université Paris 13, UFR SMBH, Bobigny, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Abdelkarim
authors.forename: Erwann
authors.initials: E
authors.lastname: Guenin
authors.forename: Odile
authors.initials: O
authors.lastname: Sainte-Catherine
authors.forename: Nadejda
authors.initials: N
authors.lastname: Vintonenko
authors.forename: Nicole
authors.initials: N
authors.lastname: Peyri
authors.forename: Gerard Yves
authors.initials: GY
authors.lastname: Perret
authors.forename: Michel
authors.initials: M
authors.lastname: Crepin
authors.forename: Abdel-Majid
authors.initials: AM
authors.lastname: Khatib
authors.forename: Marc
authors.initials: M
authors.lastname: Lecouvey
authors.forename: Mélanie
authors.initials: M
authors.lastname: Di Benedetto
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004164:Diphosphonates / Q000737:chemistry* / Q000494:pharmacology*; D004951:Esterification; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000517:prevention & control*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates