Synthesis and biological activity of isoprenoid bisphosphonates

Larry W. Shull, Andrew J. Wiemer, Raymond J. Hohl, David F. Wiemer

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Bisphosphonates have been used in the clinic to treat osteoporosis and to reduce bone resorption and the accompanying pathological bone fractures that attend a number of malignancies including multiple myeloma and cancers of the prostate, breast, and lung. There is also evidence that some bisphosphonates have direct anticancer activity. Expansion of the current class of bisphosphonates may lead to compounds that more selectively and potently target these cancers through inhibition of the mevalonate pathway. To this end, a set of dialkyl bisphosphonates bearing isoprenoid chains of varying lengths has been synthesized. Some of these compounds were found to have biological activity on post-translational processing of the oncogenic small GTPases, Ras and Rap1a, in human-derived K562 leukemia cells. Most importantly, these compounds impair protein geranylgeranylation and not protein farnesylation.

Original languageEnglish (US)
Pages (from-to)4130-4136
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number12
DOIs
StatePublished - Jun 15 2006

Fingerprint

Terpenes
Diphosphonates
Bioactivity
Protein Prenylation
Bone
Bearings (structural)
Mevalonic Acid
Spontaneous Fractures
Monomeric GTP-Binding Proteins
K562 Cells
Bone Fractures
Bone Resorption
Multiple Myeloma
Osteoporosis
Lung Neoplasms
Neoplasms
Prostatic Neoplasms
Leukemia
Proteins
Breast Neoplasms

All Science Journal Classification (ASJC) codes

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

Cite this

Shull, Larry W. ; Wiemer, Andrew J. ; Hohl, Raymond J. ; Wiemer, David F. / Synthesis and biological activity of isoprenoid bisphosphonates. In: Bioorganic and Medicinal Chemistry. 2006 ; Vol. 14, No. 12. pp. 4130-4136.
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Synthesis and biological activity of isoprenoid bisphosphonates. / Shull, Larry W.; Wiemer, Andrew J.; Hohl, Raymond J.; Wiemer, David F.

In: Bioorganic and Medicinal Chemistry, Vol. 14, No. 12, 15.06.2006, p. 4130-4136.

Research output: Contribution to journalArticle

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