Asperopiperazines A and B: Antimicrobial and Cytotoxic Dipeptides from a Tunicate-Derived Fungus Aspergillus sp. DY001.

Investigation of the cytotoxic fractions of the ethyl acetate extract of the fermentation broth of the tunicate-derived Aspergillus sp. DY001 afforded two new dipeptides, asperopiperazines A and B ( 1 and 2 ), along with the previously reported compounds (+)-citreoisocoumarin ( 3 ) and (-)-6,8-di- O -methylcitreoisocoumarin ( 4 ). Analyses of the 1D and 2D NMR spectroscopic data of the compounds supported their structural assignments. Asperopiperazine A ( 1 ) is a cyclic dipeptide of leucine and phenylalanine moieties, which are substituted with an N -methyl and an N -acetyl group, respectively. On the other hand, asperopiperazine B ( 2 ) is a cyclic dipeptide of proline and phenylalanine moieties with a hydroxyl group at C-2 of the proline part. The absolute configuration of the amino acid moieties in 1 and 2 were determined by Marfey's analyses and DFT NMR chemical shift calculations, leading to their assignment as cyclo(l- N Me-Leu-l- N Ac-Phe) and cyclo(d-6-OH-Pro-l-Phe), respectively. Asperopiperazines A and B displayed higher antimicrobial effects against Escherichia coli and Staphylococcus aureus than Candida albicans. Furthermore, compounds 1 - 4 displayed variable growth inhibitory effects towards HCT 116 and MDA-MB-231 cells, with asperopiperazine A as the most active one towards HCT 116.