Sclerotiorin (CAS: 549-23-5)

Sclerotiorin is a chlorinated azaphilone first reported from Penicillium sclerotiorum in 1940. Biochemical studies demonstrated that sclerotiorin noncompetitively inhibits the eukaryotic-like Ser/Thr protein kinase PknG from Mycobacterium tuberculosis (IC50 = 76.5 µM; KD = 11.4 µM), impairing intracellular mycobacterial survival in macrophages and enhancing rifampicin efficacy without host cytotoxicity. Independently, sclerotiorin delays both seeded and unseeded Aβ42 fibrillogenesis by kinetically stabilizing small oligomers with low β-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.