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Published on: January 22, 2019
Novel benzimidazole phosphonates as potential inhibitors of protein prenylation
Nazmul H Bhuiyan1, Michelle L Varney2, David F Wiemer3
1Department of Chemistry, University of Iowa, Iowa City, IA 52242-1294, USA.
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.
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