Asperterrestide A, a Cytotoxic Cyclic Tetrapeptide from the Marine-Derived Fungus <italic>Aspergillus terreus</italic> SCSGAF0162

A new cytotoxic and antiviral cyclic tetrapeptide, asperterrestide A (1), a new alkaloid, terremide C (2), and a new aromatic butenolide, aspernolide E (3), together with 10 known compounds were isolated from the fermentation broth of the marine-derived fungus Aspergillus terreus SCSGAF0162. Their structures were elucidated by spectroscopic analysis, and the absolute configuration of 1 was determined by the Mosher ester technique and analysis of the acid hydrolysates using a chiralphase HPLC column. Compound 1 contains a rare 3-OH-N-CH3-Phe residue and showed cytotoxicity against U937 and MOLT4 human carcinoma cell lines and inhibitory effects on influenza virus strains H1N1 and H3N2. M microorganisms have proved to be an important source of pharmacologically active metabolites, and a growing number of marine-derived fungi have been reported to produce metabolites with unique structures and interesting biological activities. The genus Aspergillus (Moniliaceae), with over 180 species, has attracted considerable attention as a rich source of alkaloids, terpenoids, xanthones, and polyketides, some of which showed antifungal, antibacterial, antifouling, and cytotoxic activities. Aspergillus terreus is commonly isolated from soil with worldwide distribution and has been found to produce a number of bioactive compounds, such as terreineol, terrain, aspulvinone, butyrolactone I, and terreic acid. With the aim of searching for novel bioactive natural compounds from marine fungi, we investigated the chemical constituents of a fermentation broth of the marine-derived fungal strain A. terreus SCSGAF0162. Three new compounds, the cyclic tetrapeptide asperterrestide A (1), the alkaloid terremide C (2), and the aromatic butenolide aspernolide E (3), together with 10 known compounds, methyl 3,4,5-trimethoxy-2-(2(nicotinamido)benzamido)benzoate (4), butyrolactone I, butyrolactone III, butyrolactone II, 4-(4-hydroxyphenyl)-5(4-hydroxyphenylmethyl)-2-hydroxyfuran-2-one, territrem C, arisugasin H, arisugasin D, territrem B, and territrem A, were isolated. Compound 1 was tested for its cytotoxicity toward human carcinoma U937, K562, BGC-823, MOLT-4, MCF-7, and A549 cell lines and antiviral activity toward two influenza virus strains. Asperterrestide A (1) was obtained as a yellowish powder. It was assigned a molecular formula of C26H32N4O5 on the basis of its HRESIMS data. Analysis of the H and C NMR spectra (Table 1) revealed the presence of three amide N-H protons (δH 6.48, 7.18, and 9.17), four methyl groups (including one Nmethyl), one methylene group, two phenyl rings, five methines (four of which were bound to heteroatoms), and four carbonyl carbons. Interpretation of the H, C, and 2D NMR data of 1 suggested a peptidic nature for the molecule. By analysis of the COSY and HMBC spectra of 1, the aromatic protons at δH 7.36 (1H, d, J = 8.0 Hz), 7.15 (1H, dd, J = 7.5, 8.0 Hz), 7.48 (1H, dd, J = 7.5, 8.0 Hz), and 8.17 (1H, d, J = 8.0 Hz) represented an ortho-disubstituted benzene ring. HMBC correlations from Received: December 22, 2012 Published: June 12, 2013 Note