Synthesis and Biological Evaluation of a Series of Aromatic Bisphospohonates




Wasko, Brian

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Bioorg Med Chem


Geminal bisphosphonates display varied biological activity depending on the nature of the substituents on the central carbon atom. For example, the nitrogenous bisphosphonates zoledronate and risedronate inhibit the enzyme farnesyl diphosphate synthase while digeranyl bisphosphonate has been shown to inhibit the enzyme geranylgeranyl diphosphate synthase. We now have synthesized isoprenoid olefins in an isoprenoid bisphosphonate and investigated the ability of these new compounds to impair protein geranylgeranylation with cells. Several of these new compounds are potent inhibitors of the enzyme geranylgeranyl diphosphate synthase.



MeSH terms Binding Sites Cell Line, Tumor Diphosphonates / chemical synthesis Diphosphonates / chemistry* Diphosphonates / pharmacology Enzyme Inhibitors / chemical synthesis* Enzyme Inhibitors / chemistry Enzyme Inhibitors / pharmacology Farnesyltranstransferase / antagonists & inhibitors Farnesyltranstransferase / metabolism Geranyltranstransferase / antagonists & inhibitors Geranyltranstransferase / metabolism Humans


Barney RJ, Wasko BM, Dudakovic A, Hohl RJ, and Wiemer DF. Synthesis and biological evaluation of a series of aromatic bisphosphonates. Bioorg Med Chem. 2010 Oct 15;18(20):7212-20.