Experimental ECD Research Articles

Lignanamides from the Roots of Metternichia macrocalyx and Their Anti-inflammatory Activity.

Five new lignanamides (1-5) and ten known amides (6-15) were isolated from the chloroform extract of Metternichia macrocalyx roots. The structures of the new compounds were elucidated via analysis of NMR spectroscopic and mass spectrometry data and known structures by comparison with data from the literature. Compound 1 had its absolute configuration established through ECD experiments, NMR calculations and quantum mechanical calculations. The anti-inflammatory activity of compounds (1-5) was assessed on RAW 264.7 macrophages. All the tested compounds reduced nitric oxide levels. In the cytokine quantification assays, only compound 2 did not significantly reduce IL-10 levels. Moreover, compounds 1-3 and 5 also reduced IL-1β levels. These results suggest the anti-inflammatory potential of these compounds.

Glycosparvine A, a new indole alkaloid from the leaves of Glycosmis parviflora

In the course of our ongoing search for biologically active compounds from medicinal plant, the ethyl acetate extract from the leaves of Glycosmis parviflora (Rutaceae) was investigated. Six compounds including a new indole alkaloid, glycosparvine A (1), and five previously known metabolites (2–6) were identified. The structure of the new compound (1) was unambiguously elucidated by spectroscopic analyses, including 1D/2D NMR spectroscopy and HRESIMS. The absolute configuration of 1 was assigned by comparing its experimental ECD spectra with those reported for similar compound in the literature. Compounds 3 and 6 exhibited moderate inhibitory effects against acetylcholinesterase (AChE) with IC50 values of 35.1 and 2.8 mM, respectively.

Ten limonoids and three protolimonoids from the Thai mangrove Xylocarpus moluccensis

Ten new limonoids, named xylomolones E–N (1−10), and two new protolimonoids, named xylomolones O (11) and P (12), were isolated from seeds of the Thai mangrove Xylocarpus moluccensis, together with the known compound, hispidone acetonide (13). The structures of these compounds were established by extensive NMR spectroscopic data, single-crystal X-ray diffraction analysis, and comparison of experimental ECD spectra. The absolute configurations of xylomolones E (1) and L (8) were unambiguously determined by single-crystal X-ray diffraction analyses, conducted with Cu Kα radiation. Xylomolones E–L (1–8) are mexicanolide-type limonoids, among which xylomolones J (6) and K (7) contain a C7/C28δ-lactone ring, whereas xylomolones M (9) and N (10) are phragmalin-type limonoids. Xylomolones O (11) and P (12) are two new protolimonoids. In addition, the 1H and 13C NMR spectroscopic data for hispidone acetonide (13) was first assigned completely. In bioassay, xylomolones F (2), M (9), and P (12) exhibited moderate inhibitory activity against the production of NO in LPS-induced RAW 264.7 cells with IC50 values of 31.54 ± 7.27, 62.84 ± 17.62, and 22.7 ± 6.56 μM, respectively.

LC–MS coupled with diagnostic ion strategy facilitated the discovery of 5-methylcoumarin meroterpenoids from Gerbera piloselloides

Plant-derived natural products remain crucial in drug development. However, the identification of undescribed natural products is becoming increasingly challenging. A comprehensive strategy combining LC–MS with diagnostic ions was proposed for the discovery of undescribed 5-methylcoumarin meroterpenoids. Thirteen undescribed 5-methylcoumarin meroterpenoids, including five pairs of enantiomers (1a/1b and 5a/5b–8a/8b), were isolated from the whole plant of Gerbera piloselloides. Their structures and absolute configurations were unambiguously determined based on their spectroscopic data, calculated and experimental ECD data and X-ray diffraction analysis. Bioassays conducted on scopolamine-induced injury PC12 cells revealed that compounds 5a/5b, 7a/7b and 8a/8b possessed mild protective effects. Additionally, compounds 2 and 8 showed notable IL-6 inhibition in lipopolysaccharide-induced BEAS-2B cells.

Two new polyketone derivatives from the mangrove endophytic fungus Aspergillus sp. GXNU TH4b

Two new polyketones, exserone B (1) and cytosporone F (2), along with three known metabolites, were isolated from the mangrove endophytic fungus Aspergillus TH4b. The structures of 1 and 2 were determined by detailed NMR, and MS spectroscopic data. The absolute configurations of 1 and 2 were determined by single crystal X-ray diffraction analysis and the combination of experimental ECD and computational ECD, respectively. Compounds 1–2 have strong inhibitory activity against citrus Psyllid (Diaphorina citri) with 95.4% and 93.7% lethal at 1000 mg/kg.

A pair of enantiotropic carbazole alkaloids from the stems of Clausena emarginata C. C. Huang

Two new carbazole alkaloids clauemarazole H (1) and clauemarazole I (2) were isolated from the stems of Clausena emarginata C. C. Huang. Their structures were confirmed by comprehensive spectroscopic analyses, and the absolute configurations were determined based on ECD experiments. The two compounds were evaluated for their neuroprotective effects against rotenone-induced damage in PC12 cells but did not exhibit any significant activity.

Xeniaphyllane and Xeniolide Diterpenes from the Deep-Sea Soft Coral Paragorgia arborea.

As exploration of ocean depths >1000 m is only possible by expensive remotely operated underwater vehicles, deep-sea invertebrates represent a largely untapped source of marine metabolites for potential applications in medicine. Our current study aims to investigate these deep-sea invertebrates in Ireland to discover new biological and chemical diversity. Here, we investigate the bubble gum coral, Paragorgia arborea, collected at 1500 m depth from Whittard canyon in the Northeastern Atlantic. This species was selected following chemical profiling and biological screening. The isolation and structure elucidation of the main metabolites yielded three new diterpenes, namely, miolenol (1) and epoxymiolenol (2) characterized by the rare bicyclo[7.2.0]undec-4-ene skeleton, and the xeniolide epoxycoraxeniolide A (3), together with five known diterpenes. The structures of the new compounds were identified through extensive NMR analysis with their absolute configurations assigned by comparison between experimental and TDDFT-calculated ECD. The eight compounds were screened for cytotoxicity and antimalarial activity, and none displayed noteworthy bioactivity.

Asperinsuterpenes A-C from the Fungus Aspergillus insuetus BTBU20220155.

Three new meroterpenoids, asperinsuterpenes A-C (1-3), and eight previously reported natural products, namely asnovolin I (4), (2'E,4'E,6'E)-6-(1'-carboxyocta-2',4',6'-triene)-9-hydroxydrim-7-ene-11,12-olide (5), (2'E,4'E,6'E)-6-(1'-carboxyocta-2',4',6'-triene)-11,12-epoxy-9,11-dihydroxydrim-7-ene (6), cinereain (7), carnequinazolines A and B (8 and 9), carnemycin B (10), and stromemycin (11) were isolated from the fungus Aspergillus insuetus, strain BTBU20220155. The structures of the compounds were determined based on spectroscopic techniques, including 1D and 2D NMR, HRESIMS, and ECD experiments. The in vitro antimicrobial evaluation revealed that compounds 5 and 11 exhibited inhibitory activity against Candida albicans, with minimum inhibitory concentration (MIC) values of 12.5 and 25 μg/mL, respectively. These findings suggest that A. insuetus is a promising source of bioactive natural products with potential applications in antifungal therapy.

Linderangolides A−D, four new butanolides from the roots of Lindera angustifolia and their cytotoxic activity

Four undescribed butanolides, linderangolides A–D (1–4), along with four known congeners, lincomolide A (5), (−)-epilitsenolide C2 (6), (−)-epilitsenolide C1 (7) and litseakolide H (8), were isolated from the roots of Lindera angustifolia. The planar structures of 1–4 were elucidated based on extensive spectroscopic analyses, the relative and absolute configurations of 1–4 were determined by the NOESY spectra and the comparison of calculated and experimental ECD. The cytotoxic activities of all isolated compounds were tested, 4 showed inhibitory activity against SGC-7 cells with IC50 value of 6.62 μM.

Triplinones A-H: Anti-Inflammatory Arylalkenyl α,β-Unsaturated-δ-Lactones Isolated from the Leaves of Australian Rainforest Plant Cryptocarya triplinervis (Lauraceae).

Our ongoing exploration of Australian rainforest plants for the biodiscovery of anti-inflammatory agents led to the isolation and structural elucidation of eight new arylalkenyl α,β-unsaturated-δ-lactones, triplinones A-H (1-8), from the leaves of the Australian rainforest plant Cryptocarya triplinervis B. Hyland (Lauraceae). The chemical structures of these compounds were established by NMR spectroscopic data analysis, while their relative and absolute configurations were established using a combination of Mosher ester analysis utilizing both Riguera's and Kishi's methods, ECD experiments, and X-ray crystallography analysis. Compounds 1-8 exhibited good inhibitory activities toward nitric oxide (NO) production in lipopolysaccharide (LPS) and interferon (IFN)-γ induced RAW 264.7 macrophages, in particular compounds 1-3 and 5, with IC50 values of 7.3 ± 0.5, 6.0 ± 0.3, 5.6 ± 0.3, and 5.4 ± 2.5 μM, respectively.

Vitifolignans, 3,4-dibenzyltetrahydrofuran lignans from Anemone vitifolia Buch.-Ham

Anemone vitifolia is a small herb found in Asia that is used to treat a range of diseases in Chinese traditional medicine. GNPS-based molecular networking of an Anemone vitifolia specimen revealed the presence of a network containing numerous ions indicating the presence of lignans, several of which suggested that there might be previously undescribed compounds in the extract. Fractionation of the organic extract yielded five undescribed lignans, the vitifolignans, together with one known. The structures were identified based on extensive spectroscopic data analysis (NMR, HR-ESI-MS, and UV), coupling constant calculation and comparison with reported data. Their absolute configurations were determined by comparison of experimental ECD spectra with calculated spectra. Compounds 4/5 showed weak inhibition of LPS-induced NO production in mouse mononuclear macrophages.

Talaesthanes A–C, three new meroterpenoids from the endophytic fungus Talaromyces primulinus H21

Three new meroterpenoids (1–3) and ten known ones (4–13) were obtained from the endophytic fungus Talaromyces primulinus H21 isolated from the plant of Euphorbia sikkimensis. Their structures including their absolute configurations were elucidated by extensive analysis of spectroscopic data such as HR-ESI-MS, 1D/2D NMR, and X-ray diffraction of single crystal together with comparison of experimental ECD with calculated ECD. All compounds were examined for their inhibitory effects on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in RAW264.7 cells, and compounds 3, 9, 12, and 13 exhibited certain inhibition on NO production, with IC50 values of 27.19, 41.55, 25.23, and 24.71 μM, respectively.

Diarylheptanoid glycosides from Dioscorea nipponica rhizomes

A group of previously undescribed diarylheptanoids with mono/di-glucose substitution, diodiarylheptosides A–F (1–6), together with six known diarylheptanoids (7–12) were isolated from the rhizomes of Dioscorea nipponica. Their structures were established by comprehensive UV, IR, HR-ESI-MS and NMR analyses, and their absolute configurations were determined by a comparison of calculated and experimental ECD, some with optical rotations, after acid-hydrolysis. Moreover, bioassay results showed that compounds 3 and 11 exhibited stronger NO inhibitions on lipopolysaccharides-induced RAW 264.7 cells, with the IC50 values of 14.91 ± 0.62 and 12.78 ± 1.12 μM.

Experimental and theoretical ECD study of the 7-methoxycoumarin-3-carboxylic acid binding to BSA

Experimental and theoretical ECD study of the 7-methoxycoumarin-3-carboxylic acid binding to BSA

Two New Lupane-Type Triterpenes From the Stems and Leaves of Buxus latistyla Gagnep. and Their Cytotoxic Activity

Objectives: This study aims to evaluate the cytotoxicity of compounds isolated from Buxus latistyla Gagnep. against selected cell lines. Methods: The isolation process was carried out using combined chromatographic techniques. The structural elucidation of compounds was achieved by combining 1D-/2D-NMR and HRESIMS data. The absolute configurations of new compounds were also confirmed using ECD experiments. The sulforhodamine B colorimetric assay was employed to assess the toxicity of isolates against tested cell lines. Results: Two new lupane-type derivatives, 3 α-carbomethoxy-3 β-hydroxy-1,3-cyclo-1,2-seco-lup-20(29)-en-1-one (1) (buxlatistylate A) and 1 α-carbomethoxy-1 β-hydroxy-1,3-cyclo-2,3-seco-lup-20(29)-en-3-one (2) (buxlatistylate B), along with five known triterpenes, including lupeol (3), lupenone (4), betulin (5), 20(29)-lupene-2 α,3 α-diol (6), and 20(29)-lupene-2 α,3 α,28-triol (7), were isolated. Compounds 1, 2, 6, and 7 exhibited weak cytotoxic activity against human cancer cells MCF-7, SK-LU-1, and SW480, with IC50 values ranging from 36.33 to 84.16 μM, whereas compounds 3-5 did not show toxicity toward tested cell lines. Conclusion: Compounds 1 and 2 are the first examples of lupane-type triterpenes containing the substituted cyclopentanone A-ring in their molecules. The biosynthetic pathways of these new compounds were also discussed and proposed herein. These findings indicate that B. latistyla holds potential for further in-depth studies on compounds with interesting structures that inhibit human cancer cells.

Four sulfur-containing compounds with anti-colon cancer effect from marine-derived fungus Aspergillus terreus

Sulfur-containing natural products possess a variety of biological functions including antitumor, antibacterial, anti-inflammatory and antiviral activities. In this study, four previously undescribed sulfur-containing compounds asperteretals L and M, terreins A and B, together with 17 known compounds were obtained from a culture of marine fungus A. terreus supplemented with inorganic sulfur source Na2SO4. Their planar structures and absolute configurations were elucidated by NMR, HRESIMS, and ECD experiments. The in vitro cytotoxicities of compounds 1–21 against HCT-116 and Caco-2 were evaluated by SRB assay. Asperteretal M (2) exhibited activity against HCT-116 with the IC50 value at 30μM. The antiproliferative effect of asperteretal M was confirmed by colony formation assay and cell death staining. Furthermore, the preliminary study on the anti-colon cancer mechanism of asperteretal M was performed by RNA-seq analysis. Western blotting validated that asperteretal M significantly decreased the expression of cell-cycle regulatory proteins CDK1, CDK4, and PCNA in a concentration-dependent manner.

Highly oxidized rearranged derivatives of quinochalcone C-glycosides from Carthamus tinctorius

Safflopentsides A−C (1−3), three highly oxidized rearranged derivatives of quinochalcone C-glycosides, were isolated from the safflower yellow pigments. Their structures were determined based on a detailed spectroscopic analysis (UV, IR, HR-ESI-MS, 1D and 2D NMR), and the absolute configurations were confirmed by the comparison of experimental ECD spectra with calculated ECD spectra. Compounds 1−3 have an unprecedented cyclopentenone or cyclobutenolide ring A containing C-glucosyl group, respectively. The plausible biosynthetic pathways of compounds have been presented. At 10 μM, 2 showed strong inhibitory activity against rat cerebral cortical neurons damage induced by glutamate and oxygen sugar deprivation.

Structurally diverse 1,2-diarylpropanes from the fruit of Crataegus pinnatifida and the investigation on their mirror-image ECD spectra with the same absolute configurations

1,2-diarylpropanes are a kind of abundant natural products formed by radical coupling. On account of molecular flexibility, it was challenged in the identifications of relative and absolute configurations of the 1,2-diarylpropanes. In this research, fourteen pairs of enantiomeric 1,2-diarylpropanes (1a/1b-14a/14b), comprising twelve previously undescribed pairs (1a/1b-4a/4b, 6a/6b-10a/10b, and 12a/12b-14a/14b), were isolated from the fruit of Crataegus pinnatifida. Their structures were determined through multiple NMR spectral analyses, empirical NMR rules, X-ray crystallography, and the comparison of experimental ECD spectra with calculated data. In addition, the analysis of ECD spectra revealed that substituent effects could generate an inverted chiroptical response, exhibiting in mirror-image ECD signals. This phenomenon was investigated by conformational analysis, molecular orbital analysis, the transition density matrix and hole/electron distributions. Moreover, a potential experimental rule was proposed for the rapid determination of the absolute configurations of the 1,2-diarylpropanes.

Antiviral Rotenoids and Isoflavones Isolated from Millettia oblata ssp. teitensis.

Three new (1-3) and six known rotenoids (5-10), along with three known isoflavones (11-13), were isolated from the leaves of Millettia oblata ssp. teitensis. A new glycosylated isoflavone (4), four known isoflavones (14-18), and one known chalcone (19) were isolated from the root wood extract of the same plant. The structures were elucidated by NMR and mass spectrometric analyses. The absolute configuration of the chiral compounds was established by a comparison of experimental ECD and VCD data with those calculated for the possible stereoisomers. This is the first report on the use of VCD to assign the absolute configuration of rotenoids. The crude leaves and root wood extracts displayed anti-RSV (human respiratory syncytial virus) activity with IC50 values of 0.7 and 3.4 μg/mL, respectively. Compounds 6, 8, 10, 11, and 14 showed anti-RSV activity with IC50 values of 0.4-10 μM, while compound 3 exhibited anti-HRV-2 (human rhinovirus 2) activity with an IC50 of 4.2 μM. Most of the compounds showed low cytotoxicity for laryngeal carcinoma (HEp-2) cells; however compounds 3, 11, and 14 exhibited low cytotoxicity also in primary lung fibroblasts. This is the first report on rotenoids showing antiviral activity against RSV and HRV viruses.

Omnipolyphilins A and B: Chlorinated Cyclotetrapeptides and Naphtho-α-pyranones from the Plant Nematode-Derived Fungus Polyphilus sieberi.

Chemical exploration for two isolates of the recently described ascomycete species Polyphilus sieberi, derived from the eggs of the plant parasitic nematode Heterodera filipjevi, afforded the identification of many compounds that belong to various metabolite families: two previously undescribed chlorinated cyclotetrapeptides, omnipolyphilins A (1) and B (2), one new pyranonaphthoquinone, ventiloquinone P (3), a 6,6'-binaphto-α-pyranone dimer, talaroderxine D (4) in addition to nine known metabolites (5-13) were isolated from this biocontrol candidate. All isolated compounds were characterized by comprehensive 1D, 2D NMR, and HR-ESI-MS analyses. The absolute configurations of the cyclotetrapeptides were determined by a combination of advanced Marfey's method, ROE correlation aided by conformational analysis, and TDDFT-ECD calculations, while ECD calculations, Mosher's method, and experimental ECD spectra were used for ventiloquinone P (3) and talaroderxine D (4). Among the isolated compounds, talaroderxine D (4) showed potent antimicrobial activities against Bacillus subtilis and Staphylococcus aureus with MIC values of 2.1 and 8.3 μg mL-1, respectively. Additionally, promising inhibitory effects on talaroderxine D (4) against the formation of S. aureus biofilms were observed up to a concentration of 0.25 μg mL-1. Moreover, ophiocordylongiiside A (10) showed activity against the free-living nematode Caenorhabditis elegans.