Novel benzimidazole phosphonates as potential inhibitors of protein prenylation

[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.

[发布日期] 2019-12-15

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