Toll-like receptor-7/8 agonist kill Leishmania amazonensis by acting as pro-oxidant and pro-inflammatory agent.

ABSTRACT:

Objectives

Evaluation of the anti-Leishmanial activity of imidazoquinoline-based TLR7/8 agonists.

Methods

TLR7/8-active imidazoquinolines (2 and 3) were synthesized and assessed for activity against Leishmania amazonensis-intracellular amastigotes using mouse peritoneal macrophages. The production of reactive oxygen species (ROS), nitric oxide (NO) and cytokines was determined in infected and non-infected macrophages.

Key findings

The imidazoquinolines, 2 and 3, were primarily agonists of TLR7 with compound 3 also showing modest TLR8 activity. Docking studies showed them to occupy the same binding pocket on TLR7 and 8 as the known agonists, imiquimod and resiquimod. Compounds 2 and 3 inhibited the growth of L. amazonensis-intracellular amastigotes with the most potent

SUBMITTER: Kaushik D 

PROVIDER: S-EPMC8359742 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature