Design and synthesis of a library of C2-substituted sulfamidoadenosines to probe bacterial permeability Journal Article
| Authors: | Zhao, S.; Maceren, J.; Chung, M.; Stone, S.; Geißen, R.; Boby, M. L.; Sherborne, B. S.; Tan, D. S. |
| Article Title: | Design and synthesis of a library of C2-substituted sulfamidoadenosines to probe bacterial permeability |
| Abstract: | Antibiotic resistance is a major threat to public health, and Gram-negative bacteria pose a particular challenge due to their combination of a low permeability cell envelope and efflux pumps. Our limited understanding of the chemical rules for overcoming these barriers represents a major obstacle in antibacterial drug discovery. Several recent efforts to address this problem have involved screening compound libraries for accumulation in bacteria in order to understand the structural properties required for Gram-negative permeability. Toward this end, we used cheminformatic analysis to design a library of sulfamidoadenosines (AMSN) having diverse substituents at the adenine C2 position. An efficient synthetic route was developed with installation of a uniform cross-coupling reagent set using Sonogashira and Suzuki reactions of a C2-iodide. The potential utility of these compounds was demonstrated by pilot analysis of selected analogues for accumulation in Escherichia coli. © 2023 Elsevier Ltd |
| Keywords: | controlled study; unclassified drug; nonhuman; drug structure; drug discovery; drug development; drug design; drug synthesis; antiinfective agent; antibiotic resistance; chemistry; anti-bacterial agents; pilot study; escherichia coli; ciprofloxacin; vancomycin; tetracycline; concentration response; reagent; cell membrane permeability; cross coupling reaction; gram-negative bacteria; diversity-oriented synthesis; permeability; iodide; bacterial membrane; daptomycin; cheminformatics; gram negative bacterium; sonogashira reaction; suzuki reaction; nucleoside derivative; adenosine derivative; article; nucleoside analogue; sulfamidoadenosine derivative |
| Journal Title: | Bioorganic & Medicinal Chemistry Letters |
| Volume: | 97 |
| ISSN: | 0960-894X |
| Publisher: | Pergamon-Elsevier Science Ltd |
| Date Published: | 2024-01-01 |
| Start Page: | 129486 |
| Language: | English |
| DOI: | 10.1016/j.bmcl.2023.129486 |
| PUBMED: | 37734424 |
| PROVIDER: | scopus |
| PMCID: | PMC10842738 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Derek S. Tan -- Source: Scopus |
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