Biological Characterization, Mechanistic Investigation and Structure-Activity Relationships of Chemically Stable TLR2 Antagonists.

ABSTRACT: Toll-like receptors (TLRs) build the first barrier in the innate immune response and therefore represent promising targets for the modulation of inflammatory processes. Recently, the pyrogallol-containing TLR2 antagonists CU-CPT22 and MMG-11 were reported; however, their 1,2,3-triphenol motif renders them highly susceptible to oxidation and excludes them from use in extended experiments under aerobic conditions. Therefore, we have developed a set of novel TLR2 antagonists (1-9) based on the systematic variation of substructures, linker elements, and the hydrogen-bonding pattern of the pyrogallol precursors by using chemically robust building blocks. The novel series of chemically stable and synthetically accessible TLR2 antagonists (1-9) was pharmacologically characterized, and the potenti

SUBMITTER: Bermudez M 

PROVIDER: S-EPMC7496872 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature