PMID- 15868957
OWN - NLM
STAT- MEDLINE
DCOM- 20050609
LR  - 20181201
IS  - 0250-7005 (Print)
IS  - 0250-7005 (Linking)
VI  - 25
IP  - 2A
DP  - 2005 Mar-Apr
TI  - Structure-activity relationships of a new class of aromatic bisphosphonates that 
      inhibit tumor cell proliferation in vitro.
PG  - 1139-45
AB  - We previously reported a simple and efficient one-pot procedure for synthesis of 
      1-hydroxymethylene-1,1-bisphosphonic acids (HMBP). According to this method, we 
      synthesized a series of new aromatic HMBP and investigated structure-activity 
      relationships by evaluating their anti-proliferative activity against A431 human 
      tumor cell line. Our results showed that the introduction of an extra methylene 
      group in a pyridyl-containing R2 side chain increased 100-fold the 
      anti-proliferative activity of the HMBP. In contrast, this chemical modification 
      did not modify the anti-proliferative activity of compounds substituted with a 
      phenyl-containing R2 side chain. Para-substitution of the phenyl ring with 
      various groups markedly influenced the HMBP activity, the order of potency 
      (bromine > chlorine > fluorine = none) closely matching the atomic volume of the 
      substituted group. Moreover, changes in the substitution position of the bromine 
      group also affected the anti-proliferative activity, the more potent activity 
      being obtained with para-substitution of the phenyl ring. In conclusion, this 
      structure-activity study led us to identify the new aromatic HMBP 
      [(4-Bromo-phenyl)-hydroxy-phosphono-methyl]-phosphonic acid as a potent in vitro 
      anti-proliferative molecule against tumor cell lines (IC50 value of 9.5 x 10(-5) 
      M). Interestingly, this compound can be further easily esterified on its 
      phosphonic acid functions according to our chemical method and, thus, represents 
      a potential candidate for the development of new esterified HMBP with enhanced 
      pharmacokinetics.
FAU - Guenin, Erwann
AU  - Guenin E
AD  - Laboratoire de Chimie Structurale Biomoleculaire (BioMoCeTi), CNRS UMR 7033, 
      Universite Paris 13, UFR SMBH, 74 rue Marcel Cachin, 93000 Bobigny, France.
FAU - Ledoux, Dominique
AU  - Ledoux D
FAU - Oudar, Olivier
AU  - Oudar O
FAU - Lecouvey, Marc
AU  - Lecouvey M
FAU - Kraemer, Michel
AU  - Kraemer M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Diphosphonates)
RN  - 15468-10-7 (hydroxymethanediphosphonic acid)
RN  - KM2Z91756Z (Risedronic Acid)
RN  - M2F465ROXU (Etidronic Acid)
SB  - IM
MH  - Antineoplastic Agents/chemical synthesis/*chemistry/*pharmacology
MH  - Carcinoma, Squamous Cell/drug therapy/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Diphosphonates/chemical synthesis/*chemistry/*pharmacology
MH  - Drug Screening Assays, Antitumor
MH  - Etidronic Acid/*analogs & derivatives/chemical synthesis/chemistry/pharmacology
MH  - Humans
MH  - Risedronic Acid
MH  - Structure-Activity Relationship
EDAT- 2005/05/05 09:00
MHDA- 2005/06/10 09:00
CRDT- 2005/05/05 09:00
PHST- 2005/05/05 09:00 [pubmed]
PHST- 2005/06/10 09:00 [medline]
PHST- 2005/05/05 09:00 [entrez]
PST - ppublish
SO  - Anticancer Res. 2005 Mar-Apr;25(2A):1139-45.