During a search for new α-glucosidase and protein tyrosine phosphatase 1B inhibitors from fungal sources, eight new secondary metabolites, including two anthranilic acid-derived peptides (1 and 2), four glycosylated anthraquinones (3−6), 4-isoprenylravenelin (7), and a dimer of 5,8-dihydroxy-4-methoxy-α-tetralone (8), along with four known compounds (9−12), were isolated from solid ricebased cultures of Malbranchea circinata. The structural elucidation of these metabolites was performed using 1D and 2D NMR techniques and DFT-calculated chemical shifts. Compounds 1−3, 9, and 10 showed inhibitory activity to yeast α-glucosidase (αGHY), with IC 50 values ranging from 57.4 to 261.3 μM (IC 50 acarbose = 585.8 μM). The effect of 10 (10.0 mg/kg) was corroborated in vivo using a sucrose tolerance test in normoglucemic mice. The most active compounds against PTP-1B were 8−10, with IC 50 values from 10.9 to 15.3 μM (IC 50 ursolic acid = 27.8 μM). Docking analysis of the active compounds into the crystal structures of αGHY and PTP-1B predicted that all compounds bind to the catalytic domains of the enzymes. Together, these results showed that M. circinata is a potential source of antidiabetic drug leads.

Fractionation of an aqueous extract from the aerial parts of Ageratina grandifolia yielded a new natural product, namely, 4-hydroxy-3-((S)-1′-angeloyloxy-(R)-2′,3′-epoxy-3′methyl)butylacetophenone (1), along with eight known compounds, including three flavonoids (2−4) and five chromenes (5− 9). NMR data interpretation and DFT-calculated chemical shifts combined with DP4+ statistical and J-DP4 probability analyses allowed for the complete characterization of compound 1. The presence of compound 1 in a plant that biosynthesizes 2,2dimethylchromenes is noteworthy, because an epoxy derivative has long been postulated as the reaction intermediate from the prenylated p-hydroxyacetophenones to cyclic dimethylchromenes. So far, this key intermediate has not been isolated, due to its purported chemical instability. Thus, this is the first report of a potential epoxide intermediate, leading to any of the chromene constituents of this plant. Compounds 1−9 inhibited yeast α-glucosidase with IC 50 values ranging from 0.79 to 460 μM (acarbose, IC 50 = 278.7 μM). The most active compounds were quercetagetin-7-O-(6-O-caffeoyl-β-D-glucopyranoside (3) and 6hydroxykaempferol-7-O-(6-O-caffeoyl-β-D-glucopyranoside (4). Kinetic analysis of 3 revealed its mixed-type inhibitor nature. Docking studies into the crystallographic structure of yeast α-glucosidase (pdb 3A4A) predicted that 3 and 4 bind at the catalytic site of the enzyme.

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Extensive fractionation of an extract from the grain-based culture of the endophytic fungus Preussia minimoides led to the isolation of two new polyketides with novel skeletons, minimoidiones A (1) and B (2), along with the known compounds preussochromone C (3), corymbiferone (4), and 5-hydroxy-2,7-dimethoxy-8-methylnaphthoquinone (5). The structures of 1 and 2 were elucidated using 1D and 2D NMR data analysis, along with DFT calculations of H NMR chemical shifts. The absolute configuration of 1 was established by a single-crystal X-ray diffraction analysis and TDDFT-ECD calculations. Compounds 1-4 significantly inhibited yeast α-glucosidase.

An infusion prepared from the aerial parts of Salvia amarissima Ortega inhibited the enzyme protein tyrosine phosphatase 1B (PTP-1B) (IC50~88 and 33 μg/mL, respectively). Phytochemical analysis of the infusion yielded amarisolide (1), 5,6,4′-trihydroxy-7,3′-dimethoxyflavone (2), 6-hydroxyluteolin (3), rutin (4), rosmarinic acid (5), isoquercitrin (6), pedalitin (7) and a new neo-clerodane type diterpenoid glucoside, named amarisolide G (8a,b). Compound 8a,b is a new natural product, and 2–6 are reported for the first time for the species. All compounds were tested for their inhibitory activity against PTP-1B; their IC50 values ranged from 62.0 to 514.2 μM. The activity was compared to that of ursolic acid (IC50 = 29.14 μM). The most active compound was pedalitin (7). Docking analysis predicted that compound 7 has higher affinity for the allosteric site of the enzyme. Gas chromatography coupled to mass spectrometry analyses of the essential oils prepared from dried and fresh materials revealed that germacrene D (15) and β-selinene (16), followed by β-caryophyllene (13) and spathulenol (17) were their major components. An ultra-high performance liquid chromatography coupled to mass spectrometry method was developed and validated to quantify amarisolide (1) in the ethyl acetate soluble fraction of the infusion of S. amarissima.