Yan-Qiong Guo

Natural thioredoxin reductase inhibitors from Jatropha integerrima

Nine new diterpenoids, jatrointelones A–I (1–9), including seven lathyranes (1–7) and two jatropholanes (8 and 9), along with 12 known analogues (10–21) were isolated from the trunks of Jatropha integerrima. The structures were elucidated by spectroscopic analysis, and the absolute configurations of 1–7 were determined by combination of single crystal X-ray diffraction, CD analysis (exciton chirality and Rh2(OCOCF3)4-induced methods), and chemical correlations. All of the isolates were screened for inhibitory activity against thioredoxin reductase (TrxR), which is a potential target for cancer chemotherapy with redox balance and antioxidant functions. Compounds 1, 3, 6, 7, and 15–21 exhibited stronger activity than the positive control, curcumin (IC50 = 25.0 μM), in which 17 and 19 represented the most active compounds with IC50 values of 9.4 and 6.8 μM, respectively. The active diterpenoids represent the rare examples of non-aromatic TrxR inhibitors from nature, and a preliminary structure–activity relationship is also proposed.

Polycyclic polyprenylated acylphloroglucinols: natural phosphodiesterase-4 inhibitors from Hypericum sampsonii

Chemical investigation of the aerial parts of Hypericum sampsonii led to the isolation of seven new polycyclic polyprenylated acylphloroglucinols, hypersampsonones A–G (1–7), together with 23 known analogs (8–30). Their structures including the absolute configurations were elucidated by combined spectroscopic analysis, quantum chemical ECD calculations, and chemical methods. Compound 1 represents an unprecedented cyclocitral monoterpene-coupled bicyclo[3.3.1]nonane skeleton, while 2 features an unusual hexahydrofuro[2,3-b]furan-diepoxy ring system fused in a tricyclo[4.3.1.15,7]undecane skeleton. All the compounds were screened by using tritium-labeled adenosine 3′,5′-cyclic monophosphate ([3H]-cAMP) as substrate for their inhibitory activity against phosphodiesterase-4 (PDE4), which is a drug target for the treatment of asthma and chronic obstructive pulmonary disease. Compounds 1, 18–19, 21, and 25–30 exhibited inhibition with IC50 values less than 10 μM, in which compound 19 represented the most active compound (IC50 = 0.64 μM), being comparable to the positive control, rolipram (IC50 = 0.62 μM).

Natural nitric oxide (NO) inhibitors from Chloranthus japonicus

Eight new lindenane sesquiterpenoid dimers, chlojapolides A-H (1-8), along with 11 known analogues were isolated from the whole plant of Chloranthus japonicus. Their structures including absolute configurations were elucidated by spectral and chemical methods. All the compounds were examined for their inhibitory effects on the nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW 264.7 macrophages, and compounds 1, 11, 13, and 17 exhibited pronounced inhibition with IC50 values in the range of 6.91-15.75μM, being more active than the positive control, quercetin (IC50=15.90μM).

Natural diarylfluorene derivatives: isolation, total synthesis, and phosphodiesterase-4 inhibition

In our previous study, selaginpulvilins A–D (1–4) featuring an unprecedented 9,9-diphenyl-1-(phenylethynyl)-9H-fluorene skeleton were identified as potent phosphodiesterase-4 (PDE4) inhibitors from Selaginella pulvinata. In the current work, a large-scale reinvestigation of the same plant led to the isolation of six additional new analogues, selaginpulvilins E–J (5–10), among which 5 features a rare 6-(4-hydroxyphenyl)-2H-pyran-2-one unit. Compounds 5–10 exhibited remarkable inhibitory activities against PDE4 with IC50 values in the range of 0.22–1.38 μM. The first total synthesis of selaginpulvilins A–F (1–6) was developed in 7–11 steps involving a Friedel–Crafts reaction as the key reaction, which provides a feasible access to this scaffold.

Chlojaponilactone B from Chloranthus japonicus: Suppression of Inflammatory Responses via Inhibition of the NF-κB Signaling Pathway

Bioassay-guided fractionation of an ethanolic extract of Chloranthus japonicus led to the isolation of the known lindenane-type sesquiterpenoid chlojaponilactone B (1). This compound exhibited pronounced inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Further anti-inflammatory assays showed that 1 suppressed the levels of some key inflammation mediators, such as iNOS, TNF-α, and IL-6, in a dose-dependent manner, and reduced the ear thickness and neutrophil infiltration in 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated mice. A mechanistic study revealed that compound 1 exerted its anti-inflammatory effects via the suppression of the NF-κB signaling pathway, which inhibited NF-κB-dependent transcriptional activity, IκBα phosphorylation, and p65 nuclear translocation. In contrast, chlojaponilactone B (1) was found to exert little influence on the MAPK signaling pathway.

Chlojapolactone A, an unprecedented 1,3-dioxolane linked-lindenane sesquiterpenoid dimer from Chloranthus japonicus

Chlojapolactone A (1), a novel lindenane sesquiterpenoid dimer with an unprecedented 1,3-dioxolane linkage, was isolated from Chloranthus japonicus. Its structure and absolute configuration was elucidated by combined spectral, computational, and chemical approaches. Compound 1 exhibited potential inhibitory effects on nitric oxide production in RAW 264.7 cells.

A new lindenane-type sesquiterpenoid lactone from Chloranthus japonicus

Abstract Chromatographic fractionation of the EtOH extracts of the Traditional Chinese Medicine (TCM) Chloranthus japonicus, has led to the isolation of a new lindenane-type sesquiterpenoid lactone derivative (1). Rosmarylchloranthalactone E (1), which consists of lindenane sesquiterpenoid lactone and rosmarinic acid moieties linked via an ester bridge, was structurally elucidated by 1D and 2D NMR and HRMS data. Compound 1 was a potent phosphodiesterase-4 (PDE4) inhibitor with an IC50 value of 0.96 ± 0.04 μM.