Penicilloneines A and B, Quinolone-Citrinin Hybrids from a Starfish-Derived Penicillium sp.

Penicilloneines A ( 1 ) and B ( 2 ) are the first reported quinolone-citrinin hybrids. They were isolated from the starfish-derived fungus Penicillium sp. GGF16-1-2, and their structures were elucidated using spectroscopic, chemical, computational, and single-crystal X-ray diffraction methods. Penicilloneines A ( 1 ) and B ( 2 ) share a common 4-hydroxy-1-methyl-2(1 H )-quinolone unit; however, they differ in terms of citrinin moieties, and these two units are linked via a methylene bridge. Penicilloneines A ( 1 ) and B ( 2 ) exhibited antifungal activities against Colletotrichum gloeosporioides , with lethal concentration 50 values of 0.02 and 1.51 μg/mL, respectively. A mechanistic study revealed that 1 could inhibit cell growth and promote cell vacuolization and consequent disruption of the fungal cell walls via upregulating nutrient-related hydrolase genes, including putative hydrolase, acetylcholinesterase, glycosyl hydrolase, leucine aminopeptidase, lipase, and beta-galactosidase, and downregulating their synthase genes 3-carboxymuconate cyclase, pyruvate decarboxylase, phosphoketolase, and oxalate decarboxylase.