Abstract
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.