Novel benzimidazole phosphonates as potential inhibitors of protein prenylation

Nazmul H. Bhuiyan, Michelle L. Varney, David F. Wiemer, Sarah A. Holstein

Research output: Contribution to journalArticle

Abstract

Benzimidazole carboxyphosphonates and bisphosphonates have been prepared and evaluated for their activity as inhibitors of protein prenylation or isoprenoid biosynthesis. The nature of the phosphonate head group was found to dictate enzyme specificity. The lead carboxyphosphonate inhibits geranylgeranyl transferase II while its corresponding bisphosphonate analogue potently inhibits farnesyl diphosphate synthase. The most active inhibitors effectively disrupted protein prenylation in human multiple myeloma cells.

Original languageEnglish (US)
Article number126757
JournalBioorganic and Medicinal Chemistry Letters
Volume29
Issue number24
DOIs
StatePublished - Dec 15 2019

Keywords

  • Benzimidazole
  • Bisphosphonate
  • Carboxyphosphonate
  • Farnesyl diphosphate synthase
  • Geranylgeranyl transferase II
  • Inhibition
  • Isoprenoid biosynthesis

ASJC Scopus subject areas

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

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