Trichothecenes from a Soil-Derived Trichoderma brevicompactum.

Six new (1-6), together with seven known (7-13), trichothecenes were isolated from the soil-derived Trichoderma brevicompactum PSU-RSPG27. Their structures were established using spectroscopic data. The structure of 1 was confirmed by X-ray data. Trichodermin (7) exhibited the most potent activity against Plasmodium falciparum (K1 strain) with an IC50 value of 0.1 µM, while other trichothecenes (1, 8, 9, and 12) were much less active, with IC50 values in the range of 7.1-9.6 µM. Compound 7 displayed activity against noncancerous Vero cells with an IC50 value of 0.4 µM. The remaining compounds showed moderate to weak activity, with IC50 values in the range of 6.9-15.3 µM. Compounds 7 and 12 were active against human oral carcinoma (KB) cells with IC50 values of 2.4 and 3.7 µM, respectively. Additionally, compounds 7 and 12 displayed antifungal activity against Candida albicans with the respective MIC values of 1 and 2 µg/mL and were active against Cryptococcus neoformans with equal MIC values of 4 µg/mL.

γ-Butyrolactone, cytochalasin, cyclic carbonate, eutypinic acid, and phenalenone derivatives from the soil fungus Aspergillus sp. PSU-RSPG185.

Purification of an extract from the broth of the soil fungus Aspergillus sp. PSU-RSPG185 resulted in the isolation of two new cyclic carbonate derivatives, aspergillusols A (1) and B (2), and one new eutypinic acid derivative, aspergillusic acid (3), along with six known secondary metabolites. Compounds 1 and 2 contain an unusual cyclic-carbonate functionality. In addition, the mycelial extract afforded two new phenalenones, aspergillussanones A (4) and B (5), one new cytochalasin, aspergilluchalasin (6), and one new γ-butyrolactone, aspergillulactone (7). Their structures were established by interpretation of spectroscopic evidence. Compound 4 exhibited weak activity toward KB and Vero cells with IC50 values of 48.4 and 34.2 µM, respectively.

Natural products with protein tyrosine phosphatase inhibitory activity.

Protein tyrosine phosphatases (PTPs) play an essential role in maintaining the proper tyrosine phosphorylation state of proteins. Abnormal tyrosine phosphorylation has been implicated in diseases as diverse as type 2 diabetes, cancer, immune disorders and neurological disorders, and thus inhibitors of PTPs have been investigated as potential treatments of these diseases. Natural products are widely regarded to be privileged structures in drug discovery efforts, and are therefore a good starting point for the development of PTP inhibitors. Here we describe reported natural product PTP inhibitors as well as methods to screen for natural product PTP inhibitors using bioassay-guided fractionation. These methods are illustrated using the example of a family of bromotyrosine-derived PTP inhibitors isolated from two marine sponges. We also identify potential pitfalls and false-positives, in particular compounds that are oxidizing agents that react irreversibly with the PTP.

Friedolanostanes and xanthones from the twigs of Garcinia hombroniana.

The twigs of Garcinia hombroniana yielded six compounds: two 17,14-friedolanostanes (garcihombronanes K-L, 1-2) and four xanthones (garcihombronones A-D, 3-6) together with 14 known compounds including four friedolanostanes, one lanostane, six xanthones, two benzoic acid derivatives and one biflavonoid. Their structures were elucidated by analysis of spectroscopic data and comparison of the NMR data with those reported previously. Their antibacterial activity against methicillin-resistant Staphylococcus aureus and S. aureus was evaluated.

Flavodonfuran: a new difuranylmethane derivative from the mangrove endophytic fungus Flavodon flavus PSU-MA201.

One new difuranylmethane derivative, flavodonfuran (1), together with tremulenolide A (2) was isolated from the mangrove-derived fungus Flavodon flavus PSU-MA201.The difuranylmethane derivative based on 1 is rare in natural products. Their structures were established by spectroscopic evidence. Compound 2 exhibited mild antibacterial and antifungal activities against Staphylococcus aureus ATCC25923 and Cryptococcus neoformans ATCC90113, respectively.

Metabolites from the mangrove-derived fungus Xylaria cubensis PSU-MA34.

Two new succinic acid derivatives, xylacinic acids A (1) and B (2), along with seven known compounds, including one succinic acid derivative (3), three mellein derivatives (4-6), cytochalasin D (7), 2-chloro-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione (8) and isosclerone (9), were isolated from the mangrove-derived fungus Xylaria cubensis PSU-MA34. Their structures were established by spectroscopic evidence. They were evaluated for cytotoxicity against KB cells and antibacterial activity against Staphylococcus aureus ATCC 25923 and methicillin-resistant S. aureus.