Malformin C

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.