A cyclopentapeptide fungal metabolite with diverse biological activities
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Malformin A is a cyclopentapeptide fungal metabolite that has been found in A. niger and has diverse biological activities. It is a plant growth regulator that induces malformations in plant structure. Malformin A inhibits replication of tobacco mosaic virus (TMV) in local lesion and leaf-disc assays (IC50s = 19.7 and 45.4 µg/ml, respectively). It is cytotoxic to NCI-H460, MIA PaCa-2, MCF-7, SF-268, and WI-38 cancer cells (IC50s = 70, 50, 100, 70, and 100 nM, respectively), inhibits proliferation of PC3 and LNCaP cells (IC50s = 130 and 90 nM, respectively), and induces apoptosis and necrosis in PC3 and LNCaP cells. Malformin A also increases the accumulation of reactive oxygen species, decreases the mitochondrial membrane potential, and induces autophagy in PC3 and LNCaP cells. It is toxic to mice when administered intraperitoneally (LD50 = 3.1 mg/kg) but not orally up to doses of 50 mg/kg.
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