Design and Synthesis of Polyphenolic Imidazo[4,5-<i>c</i>]quinoline Derivatives to Modulate Toll Like Receptor-7 Agonistic Activity and Adjuvanticity.

ABSTRACT: TLR-7/8 agonists are a well-known class of vaccine adjuvants, with a leading example now included in Covaxin, a licensed human COVID-19 vaccine. This thereby provides the opportunity to develop newer, more potent adjuvants based on structure-function studies of these classes of compounds. Imidazoquinoline-based TLR7/8 agonists are the most potent, but when used as a vaccine adjuvant side effects can arise due to diffusion from the injection site into a systemic circulation. In this work, we sought to address this issue through structural modifications in the agonists to enhance their adsorption capacity to the classic adjuvant alum. We selected a potent TLR7-selective agonist, BBIQ (EC₅₀ = 0.85 μM), and synthesized polyphenolic derivatives to assess their TLR7 agonistic activity

SUBMITTER: Kumar K 

PROVIDER: S-EPMC11249636 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature