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Benzimidazole-2-one : a novel anchoring principle for antagonizing p53-Mdm2
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Benzimidazole-2-one : a novel anchoring principle for antagonizing p53-Mdm2
Bibliographic description
| title: | Benzimidazole-2-one : a novel anchoring principle for antagonizing p53-Mdm2 |
| author: | Wang Wei, Cao Haiping, Wolf Siglinde, Camacho-Horvitz Miguel S., Holak Tadeusz  , Dömling Alexander |
| journal title: | Bioorganic & Medicinal Chemistry |
| volume: | 21 |
| issue: | 14 |
| date of publication : | 2013 |
| pages: | 3982-3995 |
| ISSN: |
0968-0896 |
| eISSN: |
1464-3391 |
| DOI: | |
| notes: | Na publikacji autor podpisany: Tad A. Holak |
| language: | English |
| journal language: | English |
| abstract in English: | Herein we propose the benzimidazole-2-one substructure as a suitable tryptophan mimic and thus a reasonable starting point for the design of p53 Mdm2 antagonists. We devise a short multicomponent reaction route to hitherto unknown 2-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)acetamides by reacting mono N-carbamate protected phenylenediamine in a Ugi-3CR followed by base induced cyclisation. Our preliminary synthesis and screening results are presented here. The finding of the benzimidazolone moiety as a tryptophan replacement in mdm2 is significant as it offers access to novel scaffolds with potentially higher selectivity and potency and improved biological activities. Observing low μM affinities to mdm2 by NMR and fluorescence polarization we conclude that the 2-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)acetamide scaffold might be a good starting point to further optimize the affinities to Mdm2. |
| keywords in English: | protein–protein interaction, ANCHOR, tryptophan, multicomponent reaction, Ugi, p53 mdm2, selectivity |
| departmental parameterization: | 30 |
| affiliation: | Wydział Chemii : Zakład Chemii Organicznej |
| type: | journal article |
| subtype: | academic paper |
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Projekt „Repozytorium otwartego dostępu do dorobku naukowego i dydaktycznego UJ” współfinansowany w ramach poddziałania 2.3.1 „Cyfrowe udostępnianie zasobów nauki” Programu Operacyjnego Polska Cyfrowa z Europejskiego Funduszu Rozwoju Regionalnego i budżetu państwa na podstawie umowy o dofinansowanie nr POPC.02.03.01-00-0030/17-00
