Triazole-based inhibitors of geranylgeranyltransferase II

Xiang Zhou, Sara V. Hartman, Ella J. Born, Jacqueline P. Smits, Sarah A Holstein, David F. Wiemer

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

A small set of triazole bisphosphonates has been prepared and tested for the ability to inhibit geranylgeranyltransferase II (GGTase II). The compounds were prepared through use of click chemistry to assemble a central triazole that links a polar head group to a hydrophobic tail. The resulting compounds were tested for their ability to inhibit GGTase II in an in vitro enzyme assay and also were tested for cytotoxic activity in an MTT assay with the human myeloma RPMI-8226 cell line. The most potent enzyme inhibitor was the triazole with a geranylgeranyl tail, which suggests that inhibitors that can access the enzyme region that holds the isoprenoid tail will display greater activity.

Original languageEnglish (US)
Pages (from-to)764-766
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume23
Issue number3
DOIs
StatePublished - Feb 1 2013

Fingerprint

Triazoles
Tail
Assays
Click Chemistry
Terpenes
Diphosphonates
Enzyme Assays
Enzyme Inhibitors
Enzymes
Cells
Cell Line
Rab geranylgeranyl transferase beta-subunit

Keywords

  • Anti-proliferative
  • Apoptosis
  • Bioassay
  • GGTase II
  • Rab GGTase

ASJC Scopus subject areas

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

Cite this

Triazole-based inhibitors of geranylgeranyltransferase II. / Zhou, Xiang; Hartman, Sara V.; Born, Ella J.; Smits, Jacqueline P.; Holstein, Sarah A; Wiemer, David F.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 23, No. 3, 01.02.2013, p. 764-766.

Research output: Contribution to journalArticle

Zhou, Xiang ; Hartman, Sara V. ; Born, Ella J. ; Smits, Jacqueline P. ; Holstein, Sarah A ; Wiemer, David F. / Triazole-based inhibitors of geranylgeranyltransferase II. In: Bioorganic and Medicinal Chemistry Letters. 2013 ; Vol. 23, No. 3. pp. 764-766.
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