Identification of 2-Aminoacyl-1,3,4-thiadiazoles as Prostaglandin E₂ and Leukotriene Biosynthesis Inhibitors.

ABSTRACT: The application of a multi-step scientific workflow revealed an unprecedented class of PGE₂/leukotriene biosynthesis inhibitors with in vivo activity. Specifically, starting from a combinatorial virtual library of ∼4.2 × 10⁵ molecules, a small set of compounds was identified for the synthesis. Among these, four novel 2-aminoacyl-1,3,4-thiadiazole derivatives (3, 6, 7, and 9) displayed marked anti-inflammatory properties in vitro by strongly inhibiting PGE₂ biosynthesis, with IC₅₀ values in the nanomolar range. The hit compounds also efficiently interfered with leukotriene biosynthesis in cell-based systems and modulated IL-6 and PGE₂ biosynthesis in a lipopolysaccharide-stimulated J774A.1 macro

SUBMITTER: Potenza M 

PROVIDER: S-EPMC9841589 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature