Conformationally constrained Ugi adducts emerge as anti-JEV antivirals
- A multicomponent Ugi library was built with carbocyclic and heterocyclic ketones to rigidify the scaffold, targeting Japanese encephalitis virus, which lacks approved antivirals.
- SAR work yielded several compounds with submicromolar-to-low-micromolar replication inhibition, good selectivity and low toxicity in Vero cells.
- A phospholipidosis assay suggested the lead's activity is not a nonspecific artifact, and docking pointed to the viral RdRp as the likely target.
💡 Points Based on the abstract
Rigidifying an Ugi scaffold is a smart way to cut the entropic penalty, but I'd want to see which ring systems actually drive potency before believing the constraint story. Docking pointing to RdRp is weak evidence on its own; a polymerase enzymatic assay, or resistance mapping, would settle it. A phospholipidosis counter-screen is a good sign for cationic amphiphilic compounds.
Design, Synthesis, and Biological Evaluations of Constrained Ugi Adducts as Anti-JEV Agents ↗