Representative LC/UV chromatogram under typical analytical conditions (C18 column; mobile phase: 5–100% ACN / H2O (0.05% H3PO4), linear gradient 20 min; flow rate: 0.2 mL/min; detection: 210 nm).
NMR Spectral Data
Representative 1H NMR (500 MHz) spectrum confirming the structure of Malformin C. Representative 13C NMR (125 MHz) spectrum supporting structural assignment of Malformin C.
Source Organism
Synthetic
Summary
Malformin C is a fungal cyclic pentapeptide with proteostasis-disrupting and cytotoxic activity.
Details
Malformin C is a disulfide-bridged cyclic pentapeptide produced by Aspergillus niger and related marine-derived strains. Initially described as a highly toxic metabolite with antibacterial activity, it has since been shown to exert potent cytotoxic effects in multiple cancer models. Mechanistically, malformin C induces reactive oxygen species (ROS) accumulation, mitochondrial dysfunction, unfolded protein response activation, and proteotoxic stress. In glioblastoma stem-like cells, it promotes aggregation of cellular proteins and blocks autophagic flux, leading to cell death. It can induce G2/M arrest and activate apoptosis-, necrosis-, and autophagy-associated pathways. In vivo xenograft models demonstrate tumor growth inhibition, although systemic toxicity limits its therapeutic window. Additionally, malformin C exhibits algicidal activity through oxidative damage mechanisms.