Novel benzimidazole phosphonates as potential inhibitors of protein prenylation

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:29

Article

Bhuiyan, Nazmul H.¹  Varney, Michelle L.²  Wiemer, David F.^1,3  Holstein, Sarah A.^2,4 

[1] Univ Iowa, Dept Chem, Iowa City, IA 52242 USA

[2] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE 68198 USA

[3] Univ Iowa, Dept Pharmacol, Iowa City, IA 52242 USA

[4] Univ Nebraska Med Ctr, Fred & Pamela Buffett Canc Ctr, Omaha, NE 68198 USA

关键词: Benzimidazole;    Farnesyl diphosphate synthase;    Geranylgeranyl transferase II;    Inhibition;    Isoprenoid biosynthesis;    Carboxyphosphonate;    Bisphosphonate;   

DOI  :  10.1016/j.bmcl.2019.126757

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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