Sesquiterpenoid Glycoside Research Articles

Bioactive secondary metabolites isolated from the branches and leaves of Pittosporum pulchrum Gagnep.

Five new compounds, including two sesquiterpenoid glycosides (1 and 2), two monoterpenoid glycosides (3 and 4), and a quinovose ester (5), together with four known compounds (6–9) were isolated from branches and leaves of Pittosporum pulchrum Gagnep. Their structures were established by 1D and 2D NMR, HR-ESI-MS, IR and UV spectral analyses. This is the first time to investigate the chemical constituents of P. pulchrum. Subsequently, the anti-inflammatory and antioxidant activities of different solvent fractions of ethanol extract and isolated compounds were evaluated. Dichloromethane and ethyl acetate fractions dramatically inhibited the production of NO in a concentration-dependent manner in LPS-induced RAW264.7 cells. Ethyl acetate and n-butanol fractions showed excellent DPPH radical scavenging activities with IC50 values of 24.31 μg/mL and 27.81 μg/mL, respectively. Compounds 7 and 8 might be potential natural antioxidants with IC50 values of 16.13 μM and 24.81 μM, respectively.

Three New Ionone Glycosides from Rhododendron capitatum Maxim.

Six ionone glycosides (1-3 and 5-7), including three new ones, named capitsesqsides A-C (1-3), together with an eudesmane sesquiterpenoid glycoside (4) and three known triterpenoid saponins (8-10) were isolated from Rhododendron capitatum. The structures of these compounds were determined by extensive spectroscopic techniques (MS, UV, 1D-NMR, and 2D-NMR) and comparison with data reported in the literature. The absolute configurations were determined by comparison of the experimental and theoretically calculated ECD curves and LC-MS analyses after acid hydrolysis and derivatization. The anti-inflammatory activities of these compounds were evaluated in the LPS-induced RAW264.7 cells. Molecular docking demonstrated that 2 has a favorable affinity for NLRP3 and iNOS.

Two new sesquiterpenoid glycoside compounds from the calyces of Physalis alkekengi L. var. franchetii (Mast.) Makino

Two new sesquiterpenoid glycosides, 8α (H)-eudesmane-1,3,11 (13)-triene-2-one -12-O-β-D-glucopyranoside (1) and dmetelisproside B (2), together with ten known compounds (3–12) were isolated from calyces of Physalis alkekengi L. var. franchetii (Mast.) Makino (PAF). Their structures were unambiguously elucidated through HR-ESI-MS, UV, IR, and NMR spectral data. Compounds 1, 10, and 12 exhibited DPPH scavenging ability with IC50 values of 33.69 ± 6.65, 6.29 ± 0.06, and 25.66 ± 3.06 μM, respectively. Additionally, 10 and 12 demonstrated weak α-glucosidase inhibition activity with IC50 values of 250.9 ± 6.60 and 347.6 ± 2.48 μM, respectively.

Sesquiterpenoids and Cytochalasins with Immunosuppressive Activity from Sonchus wightianus.

The plant species, Sonchus wightianus DC., was historically used in China for both medicinal and dietary uses. In present study, seven new guaiane sesquiterpenoids (1-7) and one cytochalasin (8), along with five known guaianes (9-13) and two known cytochalasins (14 and 15), were isolated from the whole plants of S. wightianus. These guaianes showed structural variations in the substituents at C-8 and/or C-15, and compounds 6 and 7 are two sesquiterpenoid glycoside derivatives. Their structures were determined by extensive analysis of spectroscopic, electronic circular dichroism, and X-ray diffraction data, and chemical method. Biological tests revealed that compounds 5 and 8 are potent and selective immunosuppressive reagents.

Three new caryophyllene-type sesquiterpenoid glycosides from Biebersteinia heterostemon maxim

Three new caryophyllene-type sesquiterpenoid glycosides were isolated from Biebersteinia heterostemon. Their structures were elucidated by comprehensive analysis of NMR and MS spectroscopic data. All the isolated compounds were evaluated for MCF-7/TAM cytotoxic activity. The results indicated that compound 1 was found to exhibit the weak cytotoxicity against MCF-7/TAM with the IC50 value of 106.4 ± 0.04 μM.

Pitsubcosides M−S: Novel antibacterial cadinane sesquiterpenoid glycoside esters from Pittosporum subulisepalum

A previous study on Pittosporum subulisepalum led to twelve novel, antibacterial eudesmane sesquiterpenoid glycoside esters (ESGEs). To continue the work on P. subulisepalum, this study focused on the exploration of cadinane sesquiterpenoid glycoside esters (CSGEs) with antibacterial activities and their mechanism of actions. Chemical exploration of the ethyl acetate (EtOAc) soluble phase of the leaves and stems of P. subulisepalum resulted in seven previously unreported cadinane sesquiterpenoid glycosides (CSGs), pitsubcosides M-S (1 −7), along with three known analogs. Based on one- and two-dimensional NMR (1D and 2D NMR), HRESIMS, and experimental/calculated electronic circular dichroism (ECD) spectroscopic analyses, the structures of the isolated compounds were elucidated. The novelty of these sesquiterpenoid glycosides was characterized by the highly esterified glycoside moieties. Compounds 1 − 5 exhibited marked inhibitory effects on Bacillus subtilis, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Bacillus cereus, Erwinia carotovora, and Pseudomonas syringae pv. actinidiae with the minimum inhibitory concentration (MIC) values of 3.13 μM− 50 μM. Of these, compounds 1 − 2 displayed significant antibacterial activity against B. subtilis (MIC = 3.13 and 6.25 μM). The live masses and the biofilms of B. subtilis were quantified after being treated with compounds 1 and 2. The preliminary antibacterial mechanism was revealed as to prevent bacterial biofilm formation or to destroy the formed cell membranes. These results indicated that CSGEs from P. subulisepalum are potential antibacterial lead agents.

Eudesmane sesquiterpenoid glycosides from the leaves of Pittosporum lenticellatum with anti-neuroinflammatory activity

Chemical investigation of the EtOAc extract of the leaves of Pittosporum lenticellatum led to the isolation of twenty-five previously undescribed eudesmane sesquiterpenoid glycosides, pitlencosides A－Y (1–25); their structures were elucidated by extensive spectroscopic analysis, including 1D and 2D NMR, HR-ESI-MS, ECD spectra, and X-ray crystallographic analysis. Among them, compounds 4, 5, 7, 8, 15 and 16 exhibited significant inhibitory effects on the production of nitric oxide in lipopolysaccharide-induced BV-2 microglial cells by suppressing the expression of inducible nitric oxide synthase and cyclooxygenase-2, with IC50 values ranging from 7.95 to 25.88 μM, which showed stereo-chemical and substituent dependents. Western blot analysis and molecular docking simulation confirmed the anti-inflammatory activity of compounds 4, 5, 7, 8, 15 and 16.

One new elemane sesquiterpenoid glycoside and five glycoglycerolipids from Pittosporum truncatum with anti-bacterial activity

One new elemane sesquiterpenoid glycoside and five glycoglycerolipids from Pittosporum truncatum with anti-bacterial activity

Sesquiterpenoids from the roots of Aucklandia costus and their anti-inflammatory activities

Five undescribed sesquiterpenoid dimers, aucklandiolides A–E (1–5), one new sesquiterpenoid glycoside, β-cyclocostunolide-15-β-D-glucopyranoside (6), and seventeen known analogues (7–23) were isolated from the roots of Aucklandia costus. Their structures were elucidated by comprehensive HRESIMS and NMR spectroscopic data analysis, and their configurations were confirmed by the computational calculations of ECD and NMR chemical shifts. Aucklandiolides A and B are the first examples of dimeric sesquiterpenoids with a unique 6/6/6/5/6/6 ring system originated from a proposed Diels–Alder cycloaddition between two eudesmane sesquiterpenoids. Besides, compounds 9–11, 20, and 22 showed significant inhibition of nitric oxide production in LPS-stimulated RAW 264.7 cells at a concentration of 20 μM.

Pitsubcosides A-L, highly esterified eudesmane sesquiterpenoid glycosides with antibacterial activity from Pittosporum subulisepalum and their mechanism.

Plants from the genus Pittosporum are traditionally used as antibacterial, antifungal and antiviral agents. A bioassay evaluation of the extract of Pittosporum subulisepalum revealed antibacterial activity. This study focused on the discovery of the antibacterial metabolism in P. subulisepalum, as well as the modes of action of its active components. A chemical investigation of an ethyl acetate (EtOAc) extract of the aerial parts of P. subulisepalum led to the isolation of 12 previously undescribed eudesmane sesquiterpenoid glycoside esters (ESGEs), pitsubcosides A-L (1-12). Their structures were elucidated by extensive spectroscopic analysis, including one- and two-dimensional NMR, high-resolution electrospray ionization mass spectrometry, electronic circular dichroism spectra and single-crystal X-ray crystallography analysis or by comparing with authentic samples. The new ESGEs were characterized by their highly esterified glycoside moieties. Among them, compounds 1-3, 5 and 8 showed a moderate inhibitory effect against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), Bacillus cereus, Bacillus subtilis, Pseudomonas syringae pv. actinidiae (Psa) and Erwinia carotovora with minimum inhibitory concentrations (MICs) ranging from 3.13 to 100 μm. Among them, compounds 3 and 5 showed remarkable antibacterial activity against S. aureus and Psa with MIC values of 6.25 and 3.13 μm, respectively. Live bacterial mass and the biofilms of S. aureus and Psa were quantified using methyl tetrazolium and crystal violet assays. Fluorescence microscopy and scanning electron microscopy experiments revealed an antibacterial mechanism of cell membrane architectural disruption. The results suggest that ESGEs possess great potential for the development of antibacterial agents to control plant pathogens. © 2023 Society of Chemical Industry.

Cover Picture: Anti‐Inflammatory Activities of Monoterpene and Sesquiterpene Glycosides from the Aqueous Extract of Artemisia annua L. (Chem. Biodiversity 3/2023)

Front Cover/Cover Picture. Artemisia annua L. is an annual herb of Asteraceae family, one of the famous traditional Chinese medicines, commonly known as “Qing Hao”. However, in Chongming District of Shanghai, it is called “Ku Cao” and has been used for women's post-natal rehabilitation for a long time. In this study, five new monoterpene glycosides (1–5) and two new sesquiterpenoid glycosides (6 and 7) were isolated from the water extract of the aerial part of A. annua. All the new compounds significantly inhibited the expression of IL-6 interleukin-6 in lipopolysaccharide-stimulated RAW 264.7 macrophages as reported by Q.-G. Wu et al. in their research article at 10.1002/cbdv.202201237. 2023 VOLUME 20 NO. 3

Farnesane sesquiterpenoids from Rubus delavayi and their anti-Trichinella spiralis activities

Two new farnesane sesquiterpenoid glycosides, rubusdelosides A and B (1 and 4), together with five known farnesane sesquiterpenoids (2, 3, and 5-7), and two known meroterpenoids (8 and 9), were isolated from water extract of the herbs of R. delavayi. Their structures were identified by the comprehensive analyses of physicochemical properties and spectroscopic data (NMR and HR-ESI-MS). Compounds 1-8 showed moderate in vivo anti-T. spiralis activities.

Norbisabolane-type sesquiterpenoid derivatives, benzofuran lignans and a phenolic glycoside from the roots of Glochidion wilsonii Hutch

Three highly oxygenated norbisabolane sesquiterpenoid glycosides (glochiwilsonosides A-C), five benzofuran lignans (glochiwilsonises A-E) and a phenolic glycoside (glochiwilsophe-noside), together with forty-one known compounds, were isolated from the roots of Glochidion wilsonii Hutch. The chemical structures of the compounds were identified by spectroscopic methods and previous literature data. Glochiwilsonoside A displayed anti-proliferative activity on A-549 and RAW 264.7 cell lines with an IC50 value of 34.5 ± 0.9 μM and CC50 value of 16.0 ± 0.9 μM, respectively. Twenty-three known compounds were reported from the genus Glochidion for the first time, and the chemotaxonomic characteristics of the isolated compounds were also summarized. The bisabolane/norbisabolane-type sesqui-terpenoid derivatives could be used as chemotaxonomic markers for G. wilsonii.

Two Novel Sesquiterpenoid Glycosides from the Rhizomes of Atractylodes lancea.

Secoatractylohexone A (1), an unprecedented secoguaiane lactone glycoside featuring 6/7 cores and dihydroxy-9-guaine-3-one 11-O-β-d-glucopyranoside (2), a 9,10-unsaturated guaiene-type glycoside possessing an uncommon scaffold, were isolated from the water-soluble portion of the ethanolic extract of Atractylodes lancea rhizomes together with five known compounds (3–7). The structures of 1 and 2 were elucidated on the basis of extensive spectroscopic data and application of the CD technique. The potential biological activities of secoatractylohexone A were predicted by network pharmacology in silico, the result of which indicated that secoatractylohexone A may be used to treat type II diabetes.

Further sesquiterpenoids from Pittosporum qinlingense and their anti-inflammatory activity

Four new sesquiterpenoid glycoside esters, Pitqinlingoside N-Q (1–4), together with eleven known metabolites (5–15), were isolated from 95% EtOH extract of the twigs, fruits and leaves of P. qinlingense. The structures of new compounds were elucidated on the basis of extensive spectroscopic analyses, including IR, UV, HRMS, NMR and electronic circular dichroism spectra. Unusal glycoside esters are characterized by the presence of polyacylated β-D-fucopyranosyl and β-d-glucopyranosyl units. Pitqinlingoside N (1), O (2), P (3), boscialin (5) and arvoside C (6) showed significant nitric oxide production inhibition in lipopolysaccharide (LPS)-induced BV-2 microglial cells with IC50 values ranging from 1.58 to 28.74 μM. Structure-activity relationships of the isolated compounds are discussed.

Chemical Constituents With Antiproliferative Activity From Pogostemon cablin (Blanco) Benth.

Two new patchoulene sesquiterpenoid glycosides (1–2), a natural patchoulane-type sesquiterpenoid (3) and a natural cadinene-type sesquiterpenoid (4), were isolated from the aerial parts of Pogostemon cablin (Blanco) Benth., together with eleven known sesquiterpenoids (5–15) and eleven known flavonoids (16–26). Their chemical structures were elucidated on the basis of spectroscopic methods, including NMR, HRESIMS, IR, and CD spectroscopic data analysis, as well as chemical hydrolysis. The isolated compounds 1–13 and 15–26 were tested for inhibitory effects on the proliferation of HepG2 cancer cells. Among them, compounds 17 and 19 displayed anti-proliferative effects against HepG2 cells with IC50 values of 25.59 and 2.30 μM, respectively. Furthermore, the flow cytometry analysis and Western blotting assays revealed that compound 19 significantly induced apoptosis of HepG2 cells by downregulating the ratio of Bcl-2/Bax and upregulating the expression of cleaved caspase-3 and cleaved caspase-9. Therefore, the potential pharmaceutical applications of P. cablin would be applied according to our study findings.

Structurally Diverse Sesquiterpenoid Glycoside Esters from Pittosporum qinlingense with Anti-neuroinflammatory Activity

Thirteen new sesquiterpenoid glycoside esters, including 11 aromadendrane-type compounds, pitqinlingosides A-K (1-11), one cadinane-type compound, pitqinlingoside L (12), and one eudesmane-type compound, pitqinlingoside M (13), together with seven known analogues (14-20) were isolated from the twigs, fruits, and leaves of Pittosporum qinlingense. Structures were elucidated by analysis of spectroscopic data, gas chromatography mass spectrometry (GC-MS), and chemical methods. The absolute configuration was confirmed by single-crystal X-ray crystallography analysis or electronic circular dichroism spectra. Unusual glycoside esters are characterized by the presence of polyacylated β-d-fucopyranosyl, β-d-glucopyranosyl, and β-d-xylopyranosyl units. Pitqinlingosides A (1), B (2), D (4), and F (6), pittosporanoside A1 acetate (14), and pittosporanoside A1 (16) showed significant nitric oxide production inhibition in lipopolysaccharide (LPS)-induced BV-2 microglial cells with IC50 values ranging from 0.95 to 24.12 μM. Structure-activity relationships of the isolated compounds are discussed.

Spirostanol and sesquiterpenoid glycosides from the rhizomes of Trillium tschonoskii

Three new spirostanol glycosides, trilliumosides K–M (1–3), one new sesquiterpenoid glycoside, tritschsesuquiside A (4), along with three known analogues (5–7) were obtained from the rhizomes of Trillium tschonoskii. The structures of new glycosides were elucidated by spectroscopic analyses (HRMS and NMR) and chemical methods. Glycosides 5–7 displayed cytotoxicities against five human cancer cell lines with IC50 values ranging from 10.5 ± 1.0 to 1.0 ± 0.2 μM, with 7 being the most cytotoxic compound with IC50 values of 1.0 ± 0.2, 2.2 ± 1.2, and 3.4 ± 0.4 μM against Huh7, CCRF-CEM, and HeLa cell lines, respectively. The flow cytometric results revealed that both 5 and 6 could induce apoptosis of HCT116 and Huh7 cells.

Two new sesquiterpenoid glycosides from the stems of Zanthoxylum armatum DC

Two new sesquiterpenoid glycosides as dihydrophaseic acid 4′-O-[6″-O-(4″′-hydroxy-3″′, 5″′-dimethoxy) benzoyl)]-β-D-glucopyranoside (1) and dihydrophaseic acid 4′-O-[6″-O-(3″′-methoxy- 4″′-hydroxy) benzoyl)]-β-D-glucopyranoside (2), were isolated from the stems of Zanthoxylum armatum in the study. The compound 1 and 2 showed moderate scavenging activity in DPPH free radical assay with IC50 values of 241 and 264 μM, respectively.

Cytotoxic Secondary Metabolites from the Endolichenic Fungus Hypoxylon fuscum.

As part of our search for new cytotoxic and antimicrobial natural products from endolichenic fungi, 19 compounds including 1 new 10-member lactone (2: ), 1 new polyacetylene glycoside (3: ), 1 new brasilane-type sesquiterpenoid glycoside (4: ), and 2 isobenzofuran-1(3H)-one derivatives (5: and 6: ) were isolated from the solid culture of the endolichenic fungus Hypoxylon fuscum. Their structures were unambiguously elucidated by NMR spectroscopic data, MS, ECD (electronic circular dichroism) calculation, and chemical methods. The cytotoxic effects on K562, SW480, and HEPG2 cell lines and the antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Candida albicans were assessed. Compounds 1, 2: , and 5: exhibited moderate cytotoxicity against K562, SW480, and HEPG2 cell lines while compounds 1, 9: , and 11: displayed weak antibacterial activity against S.aureus.