A Very Deep Graph Convolutional Network for 13C NMR Chemical Shift Calculations with Density Functional Theory Level Performance for Structure Assignment.

Nuclear magnetic resonance (NMR) chemical shift calculations are powerful tools for structure elucidation and have been extensively employed in both natural product and synthetic chemistry. However, density functional theory (DFT) NMR chemical shift calculations are usually time-consuming, while fast data-driven methods often lack reliability, making it challenging to apply them to computationally intensive tasks with a high requirement on quality. Herein, we have constructed a 54-layer-deep graph convolutional network for 13C NMR chemical shift calculations, which achieved high accuracy with low time-cost and performed competitively with DFT NMR chemical shift calculations on structure assignment benchmarks. Our model utilizes a semiempirical method, GFN2-xTB, and is compatible with a broad variety of organic systems, including those composed of hundreds of atoms or elements ranging from H to Rn. We used this model to resolve the controversial J/K ring junction problem of maitotoxin, which is the largest whole molecule assigned by NMR calculations to date. This model has been developed into user-friendly software, providing a useful tool for routine rapid structure validation and assignation as well as a new approach to elucidate the large structures that were previously unsuitable for NMR calculations.

The ethnopharmacology, phytochemistry and pharmacology of the genus Hericium.

ETHNOPHARMACOLOGICAL RELEVANCE: Mushrooms in the genus Hericium are used as functional food and traditional medicines for a long history in East Asian countries such as China, India, Japan, and Korea. Some species of Hericium are called as monkey head mushroom (Houtougu) in China and Yamabushitake in Japan, which are traditionally considered as rare and precious health promoting food and medicinal materials for the treatment of dyspepsia, insomnia, chronic gastritis, and digestive tract tumors. THE AIM OF THE REVIEW: This review aims to summarize the ethnopharmacology and structural diversity of secondary metabolites from Hericium species, as well as the pharmacological activities of the crude extracts and pure compounds from Hericium species in recent years. MATERIALS AND METHODS: All the information was gathered by searching Scifinder, PubMed, Web of Science, ScienceDirect, Springer, Wiley, ACS, CNKI, Baidu Scholar, Google Scholar databases and other published materials (books and Ph.D. and M. Sc. Dissertations) using the keywords "Hericium", "Traditional uses", "Chemical composition", "Quality control" and "Pharmacological activity" (1971-May 2023). The species name was checked with https://www.mycobank.org/. RESULTS: The traditional uses of Hericium species were summarized, and 230 secondary metabolites from Hericium species were summarized and classified into six classes, mainly focusing on their chemical diversity, biosynthesis, biological activities. The modern pharmacological experiments in vivo or in vitro on their crude and fractionated extracts showed that the chemical components from Hericium species have a broad range of bioactivities, including neuroprotective, antimicrobial, anticancer, α-glucosidase inhibitory, antioxidant, and anti-inflammatory activities. CONCLUSIONS: The secondary metabolites discovered from Hericium species are highly structurally diverse, and they have the potential to be rich resources of bioactive fungal natural products. Moreover, the unveiled bioactivities of their crude extracts and pure compounds are closely related to critical human health concerns, and in-depth studies on the potential lead compounds, mechanism of pharmacological effects and pharmaceutical properties are clearly warranted.

A new abietane diterpenoid from Lycopodium complanatum.

A new abietane diterpenoid, 1ß, 11-epoxyabieta-12-hydroxy-8, 11, 13-triene-7-one (1), along with three known compounds (2-4), was isolated from Lycopodium complanatum. Their structures were confirmed by the analysis of 1D, 2D NMR and HRESIMS data, and comparison with previous spectral data. All compounds were tested for inhibitory activities against A549, HepG2 and MCF-7 tumor cell lines. [Figure: see text].

Liver-cell protective pyridones from the fungi Tolypocladium album dws120.

Five previously undescribed pyridone derivatives, tolypyridones I-M, were identified from the solid rice medium fermented by Tolypocladium album dws120, along with two known compounds tolypyridone A (or trichodin A) and pyridoxatin. Their planar structures and partial relative configurations have been determined by careful interpretation of their spectroscopic data. The full assignment of the relative and absolute configurations of tolypyridones I-M was achieved by gauge-independent atomic orbital 13C NMR calculation, quantitative nuclear Overhauser effects based interatomic distance calculation, and electronic circular dichroism calculation. In addition, we have fully determined the configuration of tolypyridone A by X-ray diffraction analysis. In bioassay, tolypyridones I was able to restore cell viability and inhibit the release of alanine aminotransferase and aspartate aminotransferase for ethanol-induced LO2 cells, suggesting its potential as a liver protective agent.

Two New C21 Steroidal Glycosides from Selaginella Braunii Baker.

Two new C21 steroidal glycosides, brapreguanes A and B (1-2) were isolated from 75 % aqueous ethanol extract of Selaginella braunii Baker. Their structures were established by spectroscopic analyses (1D/2D NMR spectra and HR-ESI-MS). The absolute configurations of sugar were elucidated by enzymatic hydrolysis and GCMS analysis. In addition, all compounds were evaluated for the anti-proliferative activities against various human cancer cells in vitro. Compounds exhibited no inhibition to various human cancer cells.

Reassignment of the structures of pestalopyrones A-D.

Pestalopyrones A-D are four unusual tricyclic pyrone derivatives with flexible chiral structures, isolated from the endophytic fungus Pestalotiopsis neglecta S3. The full elucidation of their structures was a challenging task, and remained unsolved in the original article. Herein, the relative configurations of pestalopyrones A and pestalopyrones B were unambiguously assigned by detailed analyses on spectroscopic data and GIAO 13C NMR calculation method with sorted training sets (STS). The planar structures of pestalopyrones C and pestalopyrones D were revised by reinterpretation of their reported spectroscopic data, and then their relative configurations were deduced by STS GIAO 13C NMR calculation and NOE analysis. The absolute configurations of all the mentioned compounds were determined by the comparison of their experimental and calculated ECD curves.

Hypoglycemic flavonoids from Selaginella tamariscina (P.Beauv.) Spring.

Six flavonoids, namely, three undescribed biflavonoids, one undescribed 8-aryl flavonoid, and two known compounds, were isolated from Selaginella tamariscina (P.Beauv.) Spring. The structures and absolute configurations of those undescribed compounds were established by NMR spectroscopy data, HRESIMS analyses and electronic circular dichroism (ECD) analyses. In addition, all the isolates were evaluated for their hypoglycemic activity in HepG2 cells. Involvenflavone H, I, and J significantly increased glucose consumption in both normal and insulin-resistant HepG2 cells. Interestingly, these three compounds can effectively upregulate the protein expression of glucokinase (GCK) and adenylate cyclases (ADCYs). These results suggested that involvenflavone H, I, and J (especially involvenflavone J) may have potent hypoglycemic activity, which also provided promising molecular targets for the treatment of diabetes.

Four new prenylflavonol glycosides from the leaves of Cyclocarya paliurus.

Four new prenylflavonol glycosides (1-4) along with two known analogues (5-6) were isolated from the leaves of Cyclocarya paliurus for the first time. The structures of these compounds were characterized by comprehensive analysis of 1 D, 2 D NMR, HRESIMS, UV data and enzymatic hydrolysis. In bioassays, compounds 1-4 were evaluated for inhibitory effects on xanthine oxidase (XOD) and effects on the inhibition of nitric oxide (NO) production in lipopolysaccharide (LPS) induced RAW264.7 cells. Moreover, compounds 1 and 2 showed outstanding XOD inhibitions with IC50 values of 18.16 ± 3.91 and 37.65 ± 5.67 µM, and exhibited inhibitions against LPS-induced NO production with IC50 values of 80.50 ± 3.09 and 82.28 ± 2.87 µM.

Identification of a new natural biflavonoids against breast cancer cells induced ferroptosis via the mitochondrial pathway.

Breast cancer is one of the major malignant tumors in females, and currently, recurrence and metastasis are the main obstacles preventing effective breast cancer treatment. Biflavonoids of secondary metabolites from plants are excellent anticancer agents to fight sensitive and resistant breast cancer cell lines. In this study, six C-3'-C-6″ biflavonoids, including one new robustaflavone A (1, RF-A) and five known robustaflavone derivatives (2-6), were isolated from Selaginella trichoclada for the first time. We aimed to evaluate the inhibitory effects of compounds 1-6 against human breast cancer MCF-7 cells. Among the six compounds, RF-A showed the strongest activity, decreasing cell viability with an IC50 value of 11.89 µΜ. Furthermore, RF-A strikingly induced MCF-7 nonapoptotic cell death through ferroptosis by enhancing the expression of VDAC2 channels and reducing the expression of Nedd4 E3 ubiquitin ligase, leading to lipid peroxidation and ROS production. The results suggested that RF-A has potential as a novel breast cancer treatment through its regulation of the mitochondrial VDAC2 and Nedd4 pathways.

Cyclocarioside O-Q, three novel seco-dammarane triterpenoid glycosides from the leaves of Cyclocarya paliurus.

Three previously undescribed seco-dammarane triterpenoid glycosides O-Q (1-3) along with two known compounds (4 and 5) were isolated and characterized from the leaves of Cyclocarya paliurus. Their structures were determined by comprehensive analysis of 1 D, 2 D NMR and HRESIMS data. Compounds 1-5 were evaluated for their inhibitory effects against human pancreatic tumor (ASPC-1), human gastric carcinoma (SNU5), liver hepatocellular carcinoma (HEPG-2) and human colon tumor (HCT116) cell lines. Among them cyclocarioside P (2) showed somewhat inhibitory activity towards those tumor cells.

Two new biflavanoids from Selaginella trichoclada Alsto.

Two new robustaflavones, (±)-trichocladabiflavone A (1) and uncinatabiflavone E (2), along with seven known biflavanoids (3-9) were isolated from the 70% EtOH extract of Selaginella trichoclada. Their structures and absolute configurations were established by extensive spectroscopic and circular dichroism (CD) analyses. Compound 1 was resoluted into optically pure enantiomers (+)-1 and (-)-1 by chiral-phase HPLC. Moreover, compounds 1 and 2 exhibited moderate cytotoxicity against A549 and HepG2 human cancer cell lines.

Triterpenoids with antiproliferative activities from the twigs and leaves of Melaleuca linariifolia.

One new pentacyclic triterpenoid, urs-12,16-dien-3-one (1), together with twelve known pentacyclic triterpenoids (2‒13), were isolated from the twigs and leaves of Melaleuca linariifolia. Their structures were characterized by their 1D- and 2 D-NMR spectra analysis and mass spectra studies. Furthermore, all isolated compounds were tested the inhibitory effect on proliferation of six human cancer cell lines in vitro, including NCI-H441, NCI-H460, A549, SKOV3, hela, and caki-1 cells. Among them, compounds 3, 5, 7, 9, 12, and 13 exhibited moderate antiproliferative activities with IC50 values ranging from 3.85 to 33.31 µM.

Cytotoxic triterpenoid glycosides from leaves of Cyclocarya paliurus.

Three previously undescribed dammarane triterpenoid glycosides (1-3) along with five known analogues (4-8) were isolated from the leaves of Cyclocarya paliurus. Their structures and configurations were determined on the basis of comprehensive spectroscopic analyses, chemical hydrolysis and DFT GIAO 13C NMR calculation. All the isolates were evaluated cytotoxic activities against seven human cancer cell lines (MCF-7, PC-3, Du145, NCI-H1975, PC-9, SKVO3 and HepG2). Moreover, compound 4 showed a wide spectrum of cytotoxicity against human cancer cells with IC50 values ranging from 11.31 to 29.51 µM.

New cytotoxic biflavones from Selaginella doederleinii.

Three new biflavones, apigenin-(3',8″)-chrysin (1), (2S)-2,3-Dihydroametoflavone 5,4'-dimethyl ether (2), and (2S)-5″,7″-Dihydroxy-2″-phenoxychromonyl-(4'″,3')-naringenin (3), together with seven known biflavones (4-10) were isolated from the 75% EtOH extract of Selaginella doederleinii. The structures of new compounds were established by application of spectroscopic methods, including 1D and 2D NMR, HRMS, and CD measurements. In addition, all new compounds were evaluated for their cytotoxic potential against three human cancer cell lines A549, MCF-7, and SMMC-7721 in vitro. Compound 2 exhibited potent cytotoxic activity with IC50 values ranging from 6.35 to 10.18 µM.

Seladelicatulasine A-G, C27 steroidal glycosides with cholinesterase inhibitory activities from Selaginella delicatula.

Seven undescribed C27 steroidal glycosides, Seladelicatulasine A-G, including six cholestanol glycosides and one spirostanol glycoside, were isolated from Selaginella delicatula. Their structures were elucidated by 1D/2D NMR spectra and HRESIMS analyses. The absolute configurations of the sugars were determined by enzymatic hydrolysis and GC/MS analyses. These cholestanol glycosides were isolated from the family Selaginellaceae for the first time. Seladelicatulasine F is characterized as a rare B-5,6-secosteroid. In addition, all the compounds were evaluated for their inhibitory activities against cholinesterase (AChE/BChE) and monoamine oxidase (MAO-A/MAO-B). These steroidal glycosides displayed selective inhibition activities on cholinesterase. Seladelicatulasine A, B and E inhibited the AChE activity with IC50 values of 0.31, 0.09, and 0.04 µM, respectively. Seladelicatulasine A and F showed the strongest inhibition activity on BChE with IC50 values of 0.37 and 0.65 µM, respectively.

New prenylflavonol glycosides with xanthine oxidase inhibitory activity from the leaves of Cyclocarya paliurus.

Eight new prenylflavonol glycosides (1-8), along with five known analogues (9-13) were isolated from the n-butanol extract of the dried leaves of Cyclocarya paliurus (family Juglandaceae) for the first time. The structures of these compounds were characterized by comprehensive analysis of 1D, 2D NMR, HRESIMS, UV data and acid hydrolysis. In bioassay, all these thirteen prenylflavonol glycosides exhibited inhibitory effects on xanthine oxidase (XOD) activity. Especially compounds 2 and 7, showed outstanding IC50 values of 31.81 ± 2.20 and 29.71 ± 3.69 µM, respectively.

Two New Abietane Diterpenoids from Selaginella moellendorffii Hieron.

Two new abietane diterpenoids, (3S,5R,10S)-3-hydroxy-12-O-demethyl-11-deoxy-19(4→3)-abeo-cryptojaponol, 12,19-dihydroxyabieta-8,11,13-trien-7-one, were isolated from Selaginella moellendorffii Hieron., together with one known abietane diterpenoid and four known tetracyclic triterpenoids. Their structures were characterized by their 1D- and 2D-NMR, ECD and mass spectral studies. All compounds were tested for their inhibitory effects on proliferation of three human cancer cells (human non-small-cell lung carcinoma cell lines A549 and human breast adenocarcinoma cell lines MDA-MB-231 and MCF-7) in vitro. Among them, three compounds displayed modest cytotoxic activities against the above three human cancer cell lines with IC50 values ranging from 16.28 to 40.67 µM.

Palhinosides A-H: Flavone Glucosidic Truxinate Esters with Neuroprotective Activities from Palhinhaea cernua.

Palhinosides A-H (1-8), new flavone glucosidic truxinate esters, including ß-truxinate and µ-truxinate forms, were isolated from Palhinhaea cernua. Their structures were elucidated by extensive spectroscopic methods and chemical analyses. The flavone glucoside cyclodimers possess a unique cyclobutane ring in their carbon scaffolds. Compounds 2-7 represent three pairs of stereoisomers (2/3, 4/5, 6/7). The protective effects of 1-8 against the damage of HT-22 cells induced by l-glutamate were evaluated, and compounds 4 and 5 showed better neuroprotective effects than the positive control, Trolox.

Pictalignans D-F, three new neolignan derivatives from Selaginella picta.

Three new neolignan derivatives (1-3), together with three known isolariciresinol derivatives (4-6) were isolated from Selaginella picta. Their structures were elucidated by spectroscopic methods (1D/2D NMR, HRESIMS and CD). All isolated compounds were assayed on the neuroprotective activity against the injury of HT-22 cells induced by L-Glutamate in vitro. All compounds displayed potent protective effect on HT-22 cells.

Two new anthraquinone derivatives and one new triarylbenzophenone analog from Selaginella tamariscina.

Two new anthraquinone derivatives, selaginones A (1) and B (2), and one new triarylbenzophenone analog, selagibenzophenone B (3), were isolated from Selaginella tamariscina (Beauv.) Spring. Their structures were established by 1D-, 2D-NMR and HR-ESI-MS data. Compounds 1 and 2 represent the uncommon examples of aryl substituted anthraquinone derivatives. Especially, compound 2 is a unique anthranone with exceptional structural feature, in which a p-hydroxyphenyl moiety is attached to the C-10 position. Compound 3 is the second naturally occurring triarylbenzophenone and showed moderate activity against SMCC-7721 and MHCC97-H cell lines with IC50 values of 39.8, 51.5 µM respectively.