Sclerotioramine

A series of 30 sclerotioramine derivatives (2-31) of the natural compound, (+)-sclerotiorin (1), has been successfully semi-synthesized by a one-step reaction with high yields (up to 80%). The structures of these new derivatives were established by extensive spectroscopic methods and single-crystal X-ray diffraction analysis for 3, 6, and 10. (+)-Sclerotiorin (1) and its semisynthetic derivatives (2-31) were evaluated for their antifouling activity. Most of them except 6, 7, 8, 12, and 28 showed potent antifouling activity against the larval settlement of the barnacle Balanus amphitrite. More interestingly, most of the aromatic amino-derivatives (13-17, 19-21, 23, 25-27, and 29-31) showed strong antifouling activity; however, only two aliphatic amino-derivatives (5 and 10) had the activity.

Three chemical epigenetic modifiers [5-azacytidine, nicotinamide, and suberoylanilide hydroxamic acid (SAHA)] were applied to induce the metabolites of Penicillium mallochii CCH01, a fungus isolated from the gut of Ectropis oblique. Metabolite profiles of P. mallochii CCH01 were obviously changed by SAHA treatment. Four metabolites (1-4), including two new natural sclerotioramine derivatives, isochromophilone XIV (1) and isochromophilone XV (2), and two known compounds, sclerotioramine (3) and (+)-sclerotiorin (4), were isolated and purified from P. mallochii CCH01 treated with SAHA. Their structures were determined by spectroscopic analyzes. Anti-phytopathogenic activities of the isolated compounds 1-4 were investigated under laboratory conditions, and compound 4 showed broad and important inhibition activities against Curvularia lunata (IC50 = 2.1 μg/mL), Curvularia clavata (IC50 = 21.0 μg/mL), Fusarium oxysporum f. sp. Mornordica (IC50 = 40.4 μg/mL), and Botryosphaeria dothidea (IC50 = 27.8 μg/mL), which were comparable to those of referenced cycloheximide, with IC50 values of 0.3, 5.0, 12.4, and 15.3 μg/mL, respectively. Ingredients 2 and 3 showed selective and potent activities against Colletotrichum graminicola with IC50 values of 29.9 and 9.7 μg/mL, respectively. Furthermore, the antibacterial bioassays showed that compounds 3 and 4 exhibited strong inhibition activities against Bacillus subtilis, with disc diameters of zone of inhibition (ZOI) of 9.1 mm for both compounds, which were a bit weaker than that of referenced gentamycin with a ZOI of 10.8 mm. Additionally, the new metabolite 1 showed a promising activity against Candida albicans (ZOI = 10.5 mm), comparable to that of positive amphotericin B with a ZOI of 23.2 mm. The present results suggest that chemical epigenetic modifier induction was a promising approach to obtaining antimicrobial metabolites encoded by silent biosynthetic genes of P. mallochii.

Two new sclerotioramines (1 and 2) and a new natural product of sclerotioramine analog (3), together with seven known compounds have been isolated from the mangrove endophytic fungus Penicillium sclerotiorin SCNU-F0040. Their structures were identified based on the 1 D, 2 D NMR and HRESIM spectra. The absolute configurations of new compounds were deduced by specific rotation data and electronic circular dichroism spectra. All the isolated new compounds were tested on anti-diabetes activity by using a-glucosidase inhibition assay and anti-inflammatory activity by using cyclooxygenase inhibition assay, respectively. Compounds 1 and 2 have a-glucosidase inhibition activity with IC50 values of 102.3 and 217.5 μM. Compound 2 shows a moderate cyclooxygenase-2 inhibitory activity with an IC50 value of 47.8 μM.