No abstract

Three new depsidones ( 1, 3, and 4), a new diaryl ether ( 5), and a new natural pyrone ( 9) (synthetically known), together with three known depsidones, nidulin ( 6), nornidulin ( 7), and 2-chlorounguinol ( 8), were isolated from the marine-derived fungus ASPERGILLUS UNGUIS CRI282-03. Aspergillusidone C ( 4) showed the most potent aromatase inhibitory activity with the IC (50) value of 0.74 µM, while depsidones 1, 3, 6- 8 inhibited aromatase with IC (50) values of 1.2-11.2 µM. It was found that the structural feature of depsidones, not their corresponding diaryl ether derivatives (e.g. 5), was important for aromatase inhibitory activity. Aspergillusidones A ( 1) and B ( 3) showed radical scavenging activity in the XXO assay with IC (50) values of 16.0 and < 15.6 µM, respectively. Compounds 1 and 3- 7 were mostly inactive or showed only weak cytotoxic activity against HuCCA-1, HepG2, A549, and MOLT-3 cancer cell lines.

Three novel dihydroisocoumarin derivatives (1-3) with antimalarial, antituberculous, and antifungal activities have been isolated by bioassay-guided fractionation from an endophytic fungus, Geotrichum sp., collected from Crassocephalum crepidioides. Structures were established as 7-butyl-6,8-dihydroxy-3(R)-pent-11-enylisochroman-1-one (1), 7-but-15-enyl-6,8-dihydroxy-3(R)-pent-11-enylisochroman-1-one (2), and 7-butyl-6,8-dihydroxy-3(R)-pentylisochroman-1-one (3) using spectroscopic data.

Cells produce proteases as inactive zymogens. Here, we demonstrate that this tactic can extend beyond proteases. By linking the N and C termini of ribonuclease A, we obstruct the active site with the amino acid sequence recognized by plasmepsin II, a highly specific protease from Plasmodium falciparum. We generate new N and C termini by circular permutation. In the presence of plasmepsin II, a ribonuclease zymogen gains approximately 10(3)-fold in catalytic activity and maintains high conformational stability. We conclude that zymogen creation provides a new and versatile strategy for the control of enzymatic activity, as well as the potential development of chemotherapeutic agents.

Five new hybrid peptide-polyketides, curvularides A-E (1-5), were isolated from the endophytic fungus Curvularia geniculata, which was obtained from the limbs of Catunaregam tomentosa. Structure elucidation for curvularides A-E (1-5) was accomplished by analysis of spectroscopic data, as well as by single-crystal X-ray crystallography. Curvularide B (2) exhibited antifungal activity against Candida albicans, and it also showed synergistic activity with a fluconazole drug.

3-Nitropropionic acid (3-NPA, 1) was found in extracts of several strains of endophytic fungi. 3-NPA (1) exhibited potent antimycobacterial activity with the minimum inhibition concentration of 3.3 microM, but was inactive against NCI-H187, BC, KB, and Vero cell lines. Endophytes were found to produce high levels of 3-NPA (1), and therefore 3-NPA (1) accumulated in certain plants may be produced by the associated endophytes. 3-NPA (1) may be used as a chemotaxonomic marker for endophytic fungi. The structure of 3-hydroxypropionic acid, a nematicidal agent, should be revised to 3-NPA (1).

No abstract

A new tyrosine-derived metabolite, aspergillusol A (4), was isolated on a gram scale, together with a methyl ester of 4-hydroxyphenylpyruvic acid oxime (5) and secalonic acid A, from the marine-derived fungus Aspergillus aculeatus CRI323-04. The tetraol in 4 was identified as erythritol by comparison of the 1H NMR spectrum of its benzoylated derivative with those of benzoylated erythritol (7) and D-threitol (8), as well as by cellulose-based chiral HPLC analysis. Aspergillusol A (4) selectively inhibited alpha-glucosidase from the yeast Saccharomyces cerevisiae, but it was inactive toward the alpha-glucosidase from the bacterium Bacillus stearothermophilus.