Records of Natural Products

Jatroidaine A (1), a new tetranortirucallane-type triterpene, and two known analogues (2−3) were isolated from the leaves and branches of Jatropha multifida. Their structures were fully elucidated by extensive spectroscopic methods and comparison to known compounds. The absolute configuration of 1 was assigned by single-crystal X-ray diffraction analysis. All compounds were evaluated for their anti-inflammatory and thioredoxin reductase (TrxR) inhibitory activities. Unfortunately, no significant activity was observed.

One new, 10, 11-dioxo-6,7α-erythraline epoxide (A1) and four known erythrinan alkaloids 10, 11-dioxo-erythraline (A2), erysodine (A3), 8-oxo-erythraline (A4) and erythraline (A5) were isolated from the 70% methanolic extract of stems of E. Corallodendron (Fabaceae). The isolated compounds were elucidated by exploiting 1D/2D NMR, and HR-ESI-MS analysis. The absolute configuration of A1 was determined by electronic circular dichroism (ECD). Mono Amine Oxidase inhibitory activity of the isolated alkaloids was investigated in vitro using kynuramine deamination assay on recombinant human MAO-A and B enzymes. The binding modes were predicted by molecular docking and the structure activity relationships of erythrinans were then evaluated. All isolated alkaloids demonstrated preferential activity against MAO-B. A1 displayed the highest potency and selectivity against MAO-B with IC50 of 25.18 μM, (SI >3.97). The selective inhibition exhibited by erythrinan alkaloids against MAO-B is in line with the expected biological impact of Erythrina in the treatment of neurodegenerative diseases and presents this chemical class as promising leads for managing AD and PD diseases.

A new hydrocinnamoyl glucoside, 1-O-(4-hydroxyhydrocinnamoyl)-β-D-glucopyranose (1), together with fifteen known glycosides, including two phenylethanoid glycosides (2–3), two cinnamoyl glycosides (4–5), six phenolic glycosides (6–11), one lignan glycoside (12) and four megastigmane glycosides (13–16) were isolated from a 95% EtOH extract of the Typhonium giganteum rhizomes. The sixteen glycosides were structurally characterized by NMR, HRESIMS, enzymatic hydrolysis and comparison with literature. Upon evaluating inhibitory activities of compounds 1–16 against mushroom tyrosinase at 25 μM, compounds 10 and 11 exhibited obvious inhibitory activities, with %inhibition values of 20.94±0.59%, 23.28±1.09%, respectively, with arbutin used as the positive control (26.21±0.58%).

Inhibition of protein disulfide isomerase (PDI) has been attempted as a promising anti-cancer strategy. However, there is still no currently available PDI inhibitors approved for clinical use. Here, we isolated seven high yield alkaloids from Stephaniae tetrandrae Radix (STR), a medical herb frequently prescribed in anti-tumor condition, and  identified two potent natural PDI inhibitors, dicentrine and dicentrinone. Among the seven alkaloids isolated, dicentrinone (1), dicentrine (2), tetrandrine (4), and fangchinoline (5) could significantly reduce cell viability in a dosage dependent manner detected by MTT assay in human hepatoma cells. To examine whether the candidate compounds are potent PDI inhibitors, we performed insulin turbidity assay and found dicentrine and dicentrinone, but not tetrandrine  and fangchinoline, could effectively inhibit PDI activity, with IC50 of 56.70 μM and 43.95 μM  respectively. Meanwhile, dicentrine and dicentrinone failed to further reduce the cell number index when co-treated with siRNA of PDI, suggesting the compounds behave as PDI inhibitors. Furthermore, dicentrinone and dicentrine have been successfully docked to the active pocket of PDI (PDB #3UEM) by molecular docking, suggesting the existence of physical interaction between compounds and PDI. Our results suggested that dicentrine and dicentrinone may be developed into safe PDI inhibitors.