Sclerotiorin

Sclerotiorin is a chlorinated azaphilone first reported from Penicillium sclerotiorum in 1940. Biochemical studies demonstrated that sclerotiorin non-competitively inhibits the eukaryotic-like Ser/Thr protein kinase PknG from Mycobacterium tuberculosis (IC50 76.5 ?M; KD 11.4 ?M), impairing intracellular mycobacterial survival in macrophages and enhancing rifampicin efficacy without host cytotoxicity. Independently, sclerotiorin delays seeded and non-seeded A?42 fibrillogenesis by kinetically stabilizing small oligomers with low ?-sheet content, resulting in reduced seeding activity and low cellular toxicity. These mechanistic findings establish sclerotiorin as a multifunctional azaphilone scaffold targeting bacterial virulence signaling and pathological amyloid assembly.