Novel benzimidazole phosphonates as potential inhibitors of protein prenylation
| Autor: | Nazmul H. Bhuiyan, Michelle L. Varney, David F. Wiemer, Sarah A. Holstein |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Benzimidazole
Geranylgeranyl Transferase medicine.medical_treatment Clinical Biochemistry Organophosphonates Protein Prenylation Pharmaceutical Science 01 natural sciences Biochemistry Article chemistry.chemical_compound Farnesyl diphosphate synthase Drug Discovery medicine Humans Molecular Biology biology 010405 organic chemistry Organic Chemistry Bisphosphonate Phosphonate 0104 chemical sciences Isoprenoid biosynthesis 010404 medicinal & biomolecular chemistry chemistry Enzyme specificity biology.protein Molecular Medicine Protein prenylation Benzimidazoles |
| Zdroj: | Bioorg Med Chem Lett |
| ISSN: | 0960-894X |
| DOI: | 10.1016/j.bmcl.2019.126757 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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