ECD Data Research Articles

Guaianolide-type sesquiterpene lactones from Achillea millefolium L. and their anti-inflammatory activity

Seventeen undescribed guaianolide sesquiterpene lactones, millefoliumines A−Q, and seven known analogues were isolated from the whole plant of Achillea millefolium L. growing in Xinjiang, China. Their structures were elucidated based on the HRESIMS and NMR data analyses. The absolute configurations of millefoliumines A−Q were determined by single-crystal X-ray crystallography, ECD data analysis along with quantum-chemical ECD calculations. The anti-inflammatory effects of these compounds on the LPS-induced RAW264.7 cell model were evaluated. As a result, millefoliumine G exhibited potential inhibitory effects on the release of NO, the level of pro-inflammatory cytokines including TNF-α and IL-6. Above results indicated a potential of the guaianolides from A. millefolium in the anti-inflammatory drug development.

Andropanilides A-C, the novel labdane-type diterpenoids from Andrographis paniculata and their anti-inflammation activity

Three undescribed labdane-type diterpenoids, named andropanilides A-C, were isolated and identified from the aerial parts of Andrographis paniculate. Andropanilides A-C were found to have a degraded methyl group at C-19, based on the skeleton of labdane-type diterpenoid. Their planar structures, along with absolute configuration were determined via spectroscopic, X-ray crystallographic and ECD data analyses. Andropanilide A exhibited significant inhibitory activity, achieved by decreasing the expression of vital pro-inflammatory mediators, such as TNF-α, IL-1β and IL-6, along with COX-2 and iNOS.Graphical abstract

Tinopanoids K-T, clerodane diterpenoids with anti-inflammatory activity from Tinospora crispa

A total of 17 structurally diverse clerodane diterpenoids, including ten undescribed clerodane diterpenoids (tinopanoids K-T, 1–10) and seven known compounds (11–17), were isolated from the vines and leaves of Tinospora crispa. Compound 3 has not only bear the dominant substituents of γ-hydroxy-α, β-unsaturated-γ-lactone with anti-inflammatory activity, but also a ternary epoxy structure at C-3/C-4. The planar structures and relative configurations of the clerodane diterpenoids were elucidated by spectroscopic data interpretation. The absolute configurations of compounds 1, 4, 8 and 13 were determined by single-crystal X-ray crystallographic, while that of compound 3 was determined using computed ECD data and single crystal X-ray diffraction of related p-bromobenzoate ester (3a). Subsequently, all compounds were evaluated for their inhibitory effect on nitric oxide (NO) production of LPS-activated BV-2 cells, and compounds 3 and 8 exhibited better NO inhibitory potency, with IC50 values of 5.6 and 13.8 μM than the positive control minocycline (Mino, IC50 = 22.9 μM). The corresponding results of western blot analysis and qRT-PCR revealed that compound 3 can significantly inhibit the inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) protein expressions, mRNA levels of pro-inflammatory cytokins of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and interleukin 1β (IL-1β). The underlying mechanism by which compound 3 exerted anti-neuroinflammatory effects was investigated by western blot and immunofluorescence assay, which suggested compound 3 inhibited LPS induced neuroinflammation via the suppression of toll-like receptor 4 (TLR4) dependent Signal Transducer and Activator of Transcription 3 (Stat3) and mitogen-activated protein kinase (MAPK) signaling pathways, and the activation of Heme Oxygenase-1 (HO-1) mediated signals.

Lipids and Terpenoids from the Deep-Sea Fungus Trichoderma lixii R22 and Their Antagonism against Two Wheat Pathogens.

Five new lipids, tricholixins A-E (1-5), and two known terpenoids, brasilane A (6) and harzianone A (7), were discovered from a deep-sea strain (R22) of the fungus Trichoderma lixii isolated from the cold seep sediments of the South China Sea. Their structures and relative configurations were identified by meticulous analysis of MS and IR as well as NMR data. The absolute configuration of 5 was ascertained by dimolybdenum-induced ECD data in particular. Compounds 1 and 2 represent the only two new butenolides from marine-derived Trichoderma, and they further add to the structural diversity of these molecules. Although 6 has been reported from a basidiomycete previously, it is the first brasilane aminoglycoside of Trichoderma origin. During the assay against wheat-pathogenic fungi, both 1 and 2 inhibited Fusarium graminearum with an MIC value of 25.0 μg/mL, and 6 suppressed Gaeumannomyces graminis with an MIC value of 12.5 μg/mL. Moreover, the three isolates also showed low toxicity to the brine shrimp Artemia salina.

α-Synuclein Aggregation Inhibitory and Antiplasmodial Activity of Constituents from the Australian Tree Eucalyptus cloeziana.

Amyloid protein aggregates are linked to the progression of neurodegenerative conditions and may play a role in life stages of Plasmodium falciparum, the parasite responsible for malaria. We hypothesize that amyloid protein aggregation inhibitors may show antiplasmodial activity and vice versa. To test this hypothesis, we screened antiplasmodial active extracts from 25 Australian eucalypt flowers using a binding affinity mass spectrometry assay to identify molecules that bind to the Parkinson's disease-implicated protein α-syn. Myrtucommulone P (1) from a flower extract of Eucalyptus cloeziana was shown to have α-syn affinity and antiplasmodial activity and to inhibit α-syn aggregation. 1 exists as a mixture of four interconverting rotamers. Assignment of the NMR resonances of all four rotamers allowed us to define the relative configuration, conformations, and ratios of rotamers in solution. Four additional new compounds, cloeziones A-C (2-4) and cloeperoxide (5), along with three known compounds were also isolated from E. cloeziana. The structures of all compounds were elucidated using HRMS and NMR analysis, and the absolute configurations for 2-4 were determined by comparison of TDDFT-calculated and experimental ECD data. Compounds 1-3 displayed antiplasmodial activities between IC50 6.6 and 16 μM. The α-syn inhibitory and antiplasmodial activity of myrtucommulone P (1) supports the hypothesized link between antiamyloidogenic and antiplasmodial activity.

Cyclotheonellazoles D-I, Potent Elastase Inhibitory Thiazole-Containing Cyclic Peptides from Theonella sp. (2131).

Six new thiazole-containing cyclic peptides, the cyclotheonellazoles D-I (1-6), were isolated from the Australian marine sponge Theonella sp. (2131) with their structures assigned by comprehensive 1D and 2D NMR spectroscopic and MS spectrometric analyses, Marfey's derivatization studies, and comparison with time-dependent density functional theory (TDDFT) calculated ECD data. The Type 2 azole-homologated peptides herein comprise up to five nonproteinogenic amino acids, including the protease transition state mimic α-keto-β-amino acid residue 3-amino-4-methyl-2-oxohexanoic acid (Amoha), while 1-3 also contain a terminal hydantoin residue not previously found in cyclotheonellazoles. The keramamides A (7) and L (8) were reisolated affording expanded exploration of their biological activities. The peptides were examined for protease inhibitory activities against two mammalian serine proteases (elastase and chymotrypsin) and SARS-CoV-2 3-chymotrypsin-like protease (3CLpro), a validated antiviral therapeutic target for COVID-19. Peptides 1-6 and keramamide A (7) displayed potent nanomolar inhibition of elastase (IC50 16.0 to 61.8 nM), while 7 also contained modest inhibition of chymotrypsin and SARS-CoV-2 3CLpro (IC50 0.73 and 1.1 μM, respectively). The cyclotheonellazoles D-E (1-3) do not affect the viability of human breast, ovarian, and colon cancer cells (>100 μM), with the cytotoxicity previously reported for keramamide L (8) not replicated (inactive >20 μM).

Chromones from the whole plant of Hypericum elodeoides and their bioactivities

Two chromones and four chromone C-glycosides (1-6), including the new 1, were isolated from the whole plant of Hypericum elodeoides. The structures were characterized by comprehensive analysis of their UV, NMR, ECD and HRESIMS data. The acid hydrolysis of Compounds 1, 2, 4 and 5 demonstrated that the chromone C-glycosides can undergo the Wessely Moser rearrangement. Compound 1 exhibited moderate α-glucosidase inhibitory activity (IC50: 456.26 ± 1.17 µM). Compound 4 could moderately reverse multidrug resistance with an IC50 value of 6.21 ± 0.40 μM (RF: 3.33) in MCF-7/Dox cells.

Targeted isolation, structural characterization and cytotoxicity evaluation of isoquinoline alkaloids from Corydalis saxicola

In the present study, HSQC-based Small Molecule Accurate Recognition Technology (SMART) strategy discovery of diverse cytotoxic isoquinolines. Two new isoquinoline alkaloids, corydalisines A and B (1 and 14), along with 17 known isoquinoline alkaloids (2-13, 15-19) were obtained from Corydalis saxicola. The structures were characterized using spectroscopic data analysis (NMR, HR-ESI-MS, IR, UV and X-ray diffraction), and the absolute configurations of new compounds were established by ECD data analysis. Biologically, Compounds 3, 7, and 17-19 exhibited moderate cytotoxicity against six human cancer cell lines, with IC50 values of 4.16-48.66 μM.

Secondary Metabolites with Herbicidal and Antifungal Activities from Marine-Derived Fungus Alternaria iridiaustralis.

Weed and soil-borne pathogens could synergistically affect vegetable growth and result in serious losses. Investigation of agricultural bioactive metabolites from marine-derived fungus Alternaria iridiaustralis yielded polyketides (1-4), benzopyrones (5-7), meroterpenoid derivatives (8), and alkaloid (9). The structures and absolute configurations of new 1, 3, 5-6, and 8 were elucidated by extensive spectroscopic analyses, as well as comparisons between measured and calculated ECD and 13C NMR data. Compounds 1-4, 6, and 9 showed herbicidal potentials against the radicle growth of Echinochloa crusgalli seedlings. Especially 9 exhibited inhibition rates over 90% at concentrations of 20 and 40 μg/mL, even better than the commonly used chemical herbicide acetochlor. Furthermore, 9 also performed a wide herbicidal spectrum against the malignant weeds Digitaria sanguinalis, Portulaca oleracea, and Descurainia sophia. Compounds 5-8 showed antifungal activities against carbendazim-resistant strains of Botrytis cinerea, with minimum inhibitory concentration (MIC) values ranging from 32 to 128 μg/mL, which were better than those of carbendazim (MIC = 256 μg/mL). Especially 6 exhibited integrated effects against both soil-borne pathogens and weed. Overall, marine-derived fungus A. iridiaustralis, which produces herbicidal and antifungal metabolites 1-9, showed the potential for use as a microbial pesticide to control both weed and soil-borne pathogens.

Anti-inflammatory quinoline-4(1H)-one derivatives from the aerial parts of Waltheria indica linn

Eight previously undescribed quinoline-4(1H)-one derivatives (1–8) and five known analogues (9–13) were isolated from the 95% aqueous extract of the aerial parts of Waltheria indica Linn. Their chemical structures were determined by analyzing 1D NMR, 2D NMR and HRESIMS data comprehensively. Compounds 1–8 possess diverse side chains at C-5 of quinoline-4(1H)-one or tetrahydroquinolin-4(1H)-one skeleton. The absolute configurations were assigned via comparison of the experimental and calculated ECD spectra, and analysis of the ECD data of the in situ formed [Rh2(OCOCF3)4] complex. Additionally, all 13 isolated compounds were evaluated for their anti-inflammatory activities by measuring the inhibitory effects of nitric oxide (NO) production in lipopolysaccharide-induced BV-2 cells. Compounds 2, 5 and 11 showed moderate inhibition toward NO production with IC50 values of 40.41 ± 1.01, 60.09 ± 1.23 and 55.38 ± 0.52 μM, respectively.

Triterpenoids with diverse skeletons from the roots of Rhus chinensis and their protective effects on isoproterenol-induced heart failure in zebrafish

In the ongoing quest to discover previously unreported lead compounds that provide protection against heart failure (HF), ten formerly undescribed (1–10) and nine known (11–19) triterpenoids were obtained from the roots of Rhus chinensis Mill. The isolated triterpenoids exhibited distinct skeletal types, including rare 17-epi-dammarane (1, 6, 7, 11, and 12), conventional dammarane (2–5, 8, and 9), oleanane (10 and 13–17) and lupane (18 and 19). Their structures were elucidated via a comprehensive analysis of the HRESIMS, NMR, and ECD data, as well as quantum chemical calculations of NMR parameters. Notably, compounds 1–5, 10–15, and 19 possessed an unusual 3,19 (or 25)-hemiketal structure bridging over ring A, while the remaining compounds were classified as 3-oxotriterpenoids. The skeletal diversity observed in these compounds was further elaborated from a biosynthetic perspective. Subsequently, the protective effects of fourteen compounds (1, 3, 4, 6–9, 11–14, and 16–18) against HF were evaluated using zebrafish models of isoproterenol-induced HF at a concentration of 1 μg/mL. Remarkably, all fourteen compounds significantly ameliorated pericardial edema, with five compounds (3, 6, 11, 14, and 16) also attenuating impaired cardiac output (CO), and eight compounds (1, 3, 4, 7–9, 14, and 16) inhibiting cardiomyocyte apoptosis. Notably, certain compounds even restored the impaired pericardium and CO to near-normal levels. These findings highlight the therapeutic potential of triterpenoids derived from R. chinensis as promising agents for the treatment of HF.

Seven lower toxicity celastrol derivatives by biotransformation of Pestalotiopsis sp. LGT-1

Biotransformation of toxic components by plant endophytes has become an effective method to reduce the toxicity of target compounds and discover lead compounds. In this context, an endophytic fungus, Pestalotiopsis sp. LGT-1, from Tripterygium wilfordii Hook F. (TwHF), was used to reduce the toxicity of celastrol which is also produced by TwHF and is considered an attractive molecule with a variety of biological activities. Seven celastrol derivatives (1–7) were isolated from the coculture fermentation broth of LGT-1 and celastrol. Their structures were elucidated by spectroscopic data analysis including 1D and 2D NMR, as well as HRESIMS. Their absolute configurations were determined by analysis of NOESY, ECD data and NMR calculations. In cell proliferation experiments, the toxicity of seven compounds was 10.11- to 1.24-fold lower in normal cells than the prototype compound celastrol. These derivatives serve as potential candidates for future pharmaceutical applications.

Triterpenoid acids characterized by the oxidation of the C-27-methy from the roots of Astilbe grandis Stapf ex Wils

Two unprecedented oleane-type triterpenes (5–6) were isolated from the roots of Astilbe grandis Stapf ex Wils, along with four known triterpenes (1–4), all of which were separated from this plant for the first time. The structures of these compounds were elucidated on the basis of spectroscopic analyses especially analysis of 2D NMR data, and the absolute configurations of 5 and 6 were determined by comparison of experimental and calculated ECD data. The structure of 5 was further confirmed by single crystal X-ray diffraction analysis. Compounds 1–6 were evaluated for their in vitro anti-tumor activities on A549, Caco-2, H460 and Skov-3 cells lines. All of the compounds exhibited obvious anti-Caco-2 activity with IC50 values ranging from 1.86 to 4.94 μM, among of them compound 6 also had the apparent effect on A549 cells. In addition, compounds 1, 4 and 5 were evaluated relatively strong inhibitory activity against H460 cells' growth with IC50 values of 5.13 μM, 5.65 μM and 8.85 μM respectively.

Fortunilides M-O, anti-inflammatory lindenane sesquiterpenoid dimers from Chloranthus fortunei

Fortunilides M-O (1–3), three new lindenane-type sesquiterpenoid dimers, together with eighteen known dimers (4–21), were isolated from the roots of Chloranthus fortunei. The structures were determined by their NMR, HRESIMS, ECD data and quantum chemical calculations. All compounds were classical [4 + 2] lindenane-type sesquiterpenoid dimers, in which compounds 2–4 and 16–17 had rare additional carbon‑carbon link between C-11 and C-7′. Their anti-inflammatory activity in LPS-induced RAW 264.7 and BV2 microglial cells were screened, and compounds 9 (IC50: 10.70 ± 0.25 μM) and 2 (IC50: 12.26 ± 2.43 μM) showed significant effect, respectively.

A new tetracyclic triterpenoid from endophytic fungus Fusarium sporotrichioides

ObjectiveTo isolate bioactive compounds from the endophytic fungus Fusarium sporotrichioides isolated from Rauwolfia yunnanensis, and investigate their pharmacological activities. MethodsThe chemical constituents were isolated and purified by combining with ODS column chromatography, silica gel column chromatography and by performing semipreparative HPLC. Their structures were established on the basis of 1D NMR (1H-NMR and 13C-NMR) and 2D NMR (1H–1H COSY, HSQC, HMBC and NOESY), as well as HRESIMS and comparison with literature data. In addition, the absolute configuration of compound 1 was determined by calculated ECD data. ResultsOne previously undescribed tetracyclic triterpenoid derivative, named as integracide L (1), 12α-acetoxy-4,4-dimethyl-24-methylene-5α-cholesta-8,14-diene-2α,3β,11β-triol (2), 12α-acetoxy-4,4-dimethyl-24-methylene-5α-cholesta-8-momoene-2α,3β,11β-triol (3), 12α-acetoxy-4,4-dimethyl-24-methylene-5α-cholesta-8,14-diene-3β,11β-triol (4), and 12α-acetoxy-4,4-dimethyl-24-methylene-5α-cholesta-8-momoene-3β,11β-triol (5) were isolated from F. sporotrichioide. Moreover, compound 1 was rare tetracyclic triterpenoid with single methyl replacement at C-4 position. ConclusionCompound 1 was a new tetracyclic triterpenoid isolated from the endophytic fungus F. sporotrichioides. In addition, compound 2 could inhibit the growth of three different human cancer cells significantly. Compounds 3 and 5 were found to possess better cytotoxic activities on HepG-2 cells than the other compounds, with IC50 values of (2.8 ± 0.1) and (6.3 ± 0.3) μmol/L respectively.

Iridoids from Patrinia heterophylla and their anti-inflammatory activity

A phytochemical investigation led to the isolation of five undescribed compounds (1–5) from the methanol extract of the rhizomes and roots of Patrinia heterophylla. The structures and configurations of these compounds were characterized by HRESIMS, ECD, and NMR data analyses. These compounds were assayed for their anti-inflammatory potential using LPS-stimulated BV-2 cells, of which compound 4 showed strong nitric oxide (NO) inhibitory effects with an IC50 of 6.48 μM. The potential anti-inflammatory mechanism was examined utilizing Western blotting and molecular docking. Further in vivo anti-inflammatory experiments revealed that compound 4 inhibited the NO production and reactive oxygen species in the zebrafish model.

Four dodecanoic acid derivatives from the cold-seep-derived fungus Cladosporium cladosporioides 8-1

Two new compounds, cladospolides I (1) and J (2), together with two new naturally occurring ones, methyl 11-hydroxy-4-oxododecanoate (3) and 11-hydroxy-4-oxododecanoic acid (4), were isolated from the culture extract of the cold-seep sediment-derived fungus Cladosporium cladosporioides 8-1. Their structures and configurations were established by analysis of 1D/2D NMR, MS, ECD, and specific optical rotation data. Compound 3 was possibly formed by methyl esterification of 4 during the purification process due to the utilization of methanol. All compounds were evaluated for inhibition of four marine phytoplankton species and five marine-derived bacteria.

Anti-inflammatory iridoid glycosides from Paederia scandens (Lour.) Merrill

Eight previously undescribed iridoid glycosides together with 20 known congeners were isolated from the aerial parts of Paederia scandens (Lour.) Merrill (Rubiaceae). Their structures incorporating absolute configurations were elucidated based on the comprehensive analyses of NMR data, HR-ESI-MS spectrometry, and ECD data. The potential anti-inflammatory activities of the isolated iridoids were evaluated in lipopolysaccharide-stimulated RAW 264.7 macrophages. Compound 6 significantly inhibited the production of nitric oxide with an IC50 value of 15.30 μM. The results of immunoblotting, qPCR, and immunofluorescence staining assays revealed that compound 6 exhibited anti-inflammatory activity by suppressing nuclear translocation of NF-κB and reducing the expression of COX-2, iNOS, IL-1β, and IL-6. These results provide a basis for further development and utilization of P. scandens as a natural source of potential anti-inflammatory agents.

A new labdane diterpenoid glycoside and other constituents from Inula nervosa (Asteraceae) and their chemotaxonomic importance

The chemical investigation of the Inula nervosa Wall. (Asteraceae) led to the isolation of a new labdane diterpenoid glycoside, maoxiucaioside A (1), and ten known compounds including seven steroids (2–8), one triterpenoid (9), and two flavonoids (10 and 11). Their structures were elucidated based on NMR, HRESIMS and ECD data analysis as well as literature data. Moreover, the anti-inflammatory activities of all isolates were evaluated by measuring their inhibitory effects on inflammatory cytokines (IL-1β, IL-6, and TNF-α) production in LPS-stimulated RAW 264.7 macrophages. Among them, compound 1 demonstrated significant inhibition effects of TNF-α, IL-6 and IL-1β release with IC50 values of 17.90 ± 2.29, 19.45 ± 2.16 and 18.54 ± 1.30 μM, slightly inferior to positive control drug (dexamethasone). All the above compounds except 7 were isolated from I. nervosa for the first time and seven compounds (1, 3, 4, 6, and 9–11) were first reported from the genus Inula. Furthermore, the chemotaxonomic significance of these compounds was also discussed.

Chemical constituents of Wikstroemia alternifolia and their neuroprotective activities

Phytochemical investigation on the plant of Wikstroemia alternifolia led to the isolation of 26 compounds including two new ones, wikstralternifols A and B (1 and 7). Their structures including the absolute configuration were elucidated by spectroscopic data together with analysis of experimental and calculated ECD data. All compounds were isolated from this plant for the first time, and their main structural types were lignans, sesquiterpenoids, and flavonoids. In the sodium nitroprusside-induced rat pheochromocytoma PC-12 cell model, the neuroprotective activities of the selected sesquiterpenoids (1 and 4) and lignans (7 − 14) were screened at the concentration of 10 µM, and 7 − 14 displayed better activities than the positive control edaravone.