Synthesis and biological evaluation of a series of aromatic bisphosphonates

Rocky J. Barney, Brian M. Wasko, Amel Dudakovic, Raymond Hohl, David F. Wiemer

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Geminal bisphosphonates display varied biological activity depending on the nature of the substituents on the central carbon atom. For example, the nitrogenous bisphosphonates zoledronate and risedronate inhibit the enzyme farnesyl diphosphate synthase while digeranyl bisphosphonate has been shown to inhibit the enzyme geranylgeranyl diphosphate synthase. We now have synthesized isoprenoid bisphosphonates where an aromatic ring has been used to replace one of the isoprenoid olefins in an isoprenoid bisphosphonate and investigated the ability of these new compounds to impair protein geranylgeranylation within cells. Several of these new compounds are potent inhibitors of the enzyme geranylgeranyl diphosphate synthase.

Original languageEnglish (US)
Pages (from-to)7212-7220
Number of pages9
JournalBioorganic and Medicinal Chemistry
Volume18
Issue number20
DOIs
StatePublished - Oct 15 2010

Fingerprint

Diphosphonates
Terpenes
Farnesyltranstransferase
zoledronic acid
Geranyltranstransferase
Protein Prenylation
Alkenes
Enzyme Inhibitors
Enzymes
Bioactivity
Carbon
Atoms
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Barney, Rocky J. ; Wasko, Brian M. ; Dudakovic, Amel ; Hohl, Raymond ; Wiemer, David F. / Synthesis and biological evaluation of a series of aromatic bisphosphonates. In: Bioorganic and Medicinal Chemistry. 2010 ; Vol. 18, No. 20. pp. 7212-7220.
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Synthesis and biological evaluation of a series of aromatic bisphosphonates. / Barney, Rocky J.; Wasko, Brian M.; Dudakovic, Amel; Hohl, Raymond; Wiemer, David F.

In: Bioorganic and Medicinal Chemistry, Vol. 18, No. 20, 15.10.2010, p. 7212-7220.

Research output: Contribution to journalArticle

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T1 - Synthesis and biological evaluation of a series of aromatic bisphosphonates

AU - Barney, Rocky J.

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AU - Wiemer, David F.

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