Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 97, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2023.129486
Keywords
Gram-negative bacteria; Antibiotic resistance; Nucleoside analogue; Diversity-oriented synthesis; Drug discovery
Categories
Ask authors/readers for more resources
Antibiotic resistance is a major threat to public health, with Gram-negative bacteria presenting unique challenges due to their low permeability and efflux pumps. Limited understanding of the chemical rules for overcoming these barriers hinders antibacterial drug discovery. Efforts to address this issue, such as screening compound libraries and using cheminformatic analysis, have led to the design of sulfamidoadenosines with diverse substituents, showing potential utility in accumulation in Escherichia coli.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available