Bioactive Natural Products from the Marine-Derived Penicillium brevicompactum OUCMDZ-4920

Abstract

© 2017 Chinese Chemical Society & SIOC, CAS. A mycophenolic acid producing strain OUCMDZ-4920, identified as Penicillium brevicompactum, was isolated from a marine sediment (-68 m) collected in South China Sea by means of intergrated chemical and bioactive screening method. Eleven compounds including mycophenolic acid (3) and its seven analogues (1, 2 and 4~8) were isolated from a nutrient-poor fermentation broth of P. brevicompactum OUCMDZ-4920, among which (±)-brevicolides A (1) and B (2) were new compounds. On the bases of spectroscopic and electronic circular dichroism (ECD) analyses, chemical transformation, chiral separation and Mosher's method, new compounds (-)-brevicolide A (1a), (+)-brevicolide A (1b), (-)-brevicolide B (2a) and (+)-brevicolide B (2b) were identified as 7-hydroxy-6-((S)-2-hydroxy-2-((R)-2-methyl-5-oxotetrahydrofuran-2-yl)ethyl)-5-methoxy-4-methylisobenzofuran-1(3H)-one, 7-hydroxy-6-((R)-2-hydroxy-2-((S)-2-methyl-5-oxotetrahydrofuran-2-yl)ethyl)-5-methoxy-4-methylisobenzofuran-1(3H)-one, 7-hydroxy-6-((S)-2-hydroxy-2-((S)-2-methyl-5-oxotetrahydrofuran-2-yl)ethyl)-5-methoxy-4-methylisobenzo-furan-1(3H)-one and 7-hydroxy-6-((R)-2-hydroxy-2-((R)-2-methyl-5-oxotetrahydro-furan-2-yl)ethyl)-5-methoxy-4-methylisobenzo-furan-1(3H)-one, respectively. And the known compounds were identified as mycophenolic acid (3), 3-hydroxymycophenolic acid (4), (S)-4-(5-hydroxy-7-methoxy-4-methyl-1-oxo-1, 3-dihydroisobenzo-furan-6-yl)-2-methylbutanoic acid (5), norpestaphthalides A (6) and B (7), 5, 7-dihydroxy-4-methylisobenzofuran-1(3H)-one (8), 6, 8-dihydroxy-3-(hydroxymethyl)-1H-isochromen-1-one (9), brevianamides A (10) and E (11), respectively. Compound 3 displayed good cytotoxicities against murine leukemia P388 cell, human oral epithelial carcinoma KB cell, human colorectal cancer HT29 cell, human breast cancer MCF-7 cell, and human lung cancer A549 cell as well as good antifungal activity against Candida albicans with the IC50 values of 0.4~5.29 μmol·L-1, and a half maximal inhibitory concentration (MIC) value of 4.7 μmol·L-1, respectively. In addition, four new compounds, (-)-7-O-methylbrevicolide A (12a), (+)-7-O-methyl-brevicolide A (12b), (-)-7-O-methyl-brevicolide B (13a) and (+)-7-O-methylbrevicolide B (13b) were also synthesized.