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.

Cytotoxic effects of the biflavonoids isolated from Selaginella trichoclada on MCF-7 cells and its potential mechanism.

A new biflavonoid, (2''S)-6''-methyl-2'',3''-dihydroochnaflavone (1), along with two known ochnaflavones (2, 3), four known amentoflavones (4-7) and two known robustaflavones (8, 9) were obtained from the 70% EtOH extract of Selaginella trichoclada. The chemical structures of isolated compounds were elucidated by extensive spectroscopic analyses. Overall, compounds 1-9 displayed moderate cytotoxic effects against human breast cancer MCF-7 cell lines. Among them, compounds 2 and 8 exhibited relatively strong cytotoxic effects against MCF-7 cells with an IC50 value of 7.7 and 6.9 µΜ, respectively. The results of RNA-sequencing and KEGG functional enrichment analysis showed that 8 could induce ferroptosis in MCF-7 cells by down-regulating the expression of ferroptosis-related genes including ACSL4, NOXO1, NOXA1, ACSL5, STEAP3, LPCAT3, ATG7 and TP53. Then 8 could inhibit the expression of ACSL4 proteins through molecule docking analysis, which showed a strong interaction of - 11.89 Kcal/mol binding energy. Those results indicate that 8 could be chemotherapy agents to fight drug resistance in breast cancer by down-regulating the expression level of ACSL4 proteins via ferroptosis, which needs to be further certified in vitro.

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.

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.

Three new isobenzofuranone derivatives from the fruiting bodies of Hericium erinaceus.

Three new isobenzofuranone derivatives erinaceolactones D-F (1-3), together with four known ones (4-7), were isolated from the fruiting bodies of Hericium erinaceus. Their structures were determined on the basis of comprehensive spectroscopic analyses including UV, 1D, 2D NMR and HR-TOF-MS. The absolute configuration of erinaceolactone D (1) and erinaceolactone E (2) were assigned by comparing their specific rotation with those of analogs in literatures. The four known compounds were isomers with each other and were isolated simultaneously for the first time.

Two new isobenzofuranone derivatives from the fruiting bodies of Hericium erinaceus.

Two new isobenzofuranone derivatives erinaceolactones G and H (1 and 2) were isolated from the ethanolic extract of fruiting bodies of Hericium erinaceus. Their structures were characterized on the basis of spectroscopic evidences. Compound 2 was suggested to be racemic by specific rotation, which was resolved by chiral HPLC into enantiomers.

Two new compounds from the green peel of Juglans mandshurica.

A new cyclic diarylheptanoid (1) and a new flavone glucoside (2), along with seven known compounds, were isolated from the green peel of Juglans mandshurica. Their structures were elucidated based on extensive spectroscopic analyses. Moreover, the cytotoxicity against NCI-H460, A549, and K562 cancer cells of compounds 1-6 was evaluated. The results showed that compound 3 exhibited moderate inhibitory potency against the growth of three cell lines.

Two new flavonoids from Selaginella uncinata.

Two new flavonoids, uncinataflavones A (1) and B (2), along with one known compound 6-(5-carboxyl-2-methoxyphenyl)-apigenin (3), were isolated from Selaginella uncinata (Desv.) Spring. All these compounds belong to apigenin derivatives with aryl substituents at C-6 position. The structures of new compounds were elucidated on the basis of comprehensive spectroscopic analyses (UV, IR, 1D, and 2D NMR as well as HR-ESI-MS).

[A new flavonoid with an aryl moiety from Selaginella uncinata].

The present study is to investigate the chemical constituents of the whole plants of Selaginella uncinata. A new flavonoid was isolated from the 75% ethanol extract of Selaginella uncinata by column chromatographies over macroporous resin, silica gel, Sephadex LH-20 and prep-HPLC. The structure was elucidated as 8-[4-(carboxyl)phenoxy]-5,4'-dihydroxy-7-methoxyflavanone (1) and named unciflacone G.

New Selaginellin derivatives from Selaginella tamariscina.

Two new selaginellin derivatives selaginellin P (1) and selaginellin Q (2) were isolated from Selaginella tamariscina. The structures of 1 and 2 were established as 2,4'-dihydroxy-4-methyl-3-[(4-hydroxyphenyl)ethynyl]biphene (1) and 2,4'-dihydroxy-3-[(4-hydroxyphenyl)ethynyl]biphene (2) on the basis of spectroscopic means including HR-ESI-MS, 1D, and 2D NMR experiments.

[Flavonoids from Selaginella uncinata].

In the current study, nine flavonoids were isolated and purified from 75% ethanol extract of Selaginella uncinata (Desv.) Spring by column chromatographic techniques over macroporous resin, polyamide, silica gel, Sephadex LH-20 and pre-HPLC. On the basis of their physico-chemical properties and spectroscopic data analyses, these compounds were elucidated as cirsimarin (1), nepitrin (2), apigenin-6-C-α-L-arabinopyranosyl-8-C-ß-D-glucopyranoside (3), apigenin-6-C-ß-D-glucopyranosyl-8-C-α-L-arabinopyranoside (4), apigenin-7-O-ß-D-glucopyranoside (5), 2,3-dihydroamentoflavone (6), 4'-O-methylamentoflavone (7), 2,3-dihydro-4'-O-methyl-amentoflavone (8), and 2,3,2",3"-tetrahydron-4'-O-methyl-robustaflavone (9). Compounds 1-5 belong to flavonoid glycosides and were isolated from the genus Selaginella for the first time.

Inhibitory effect of reinioside C on vascular smooth muscle cells proliferation induced by angiotensin II via inhibiting NADPH oxidase-ROS-ENK1/2-NF-kappaB-AP-1 pathway.

The proliferation of vascular smooth muscle cells (VSMCs) induced by angiotensin II (Ang II) plays a vital role in the pathogenesis of arteriosclerosis and restenosis. In the present study, the effect of reinioside C, a main active ingredient of Polygala fallax Hemsl, on proliferation of VSMCs induced by Ang II was investigated. It was found that Ang II (1 microM) markedly stimulated proliferation of VSMCs. Pretreatment of reinioside C (3, 10 or 30 microM) concentration-dependently inhibited the proliferative effect of Ang II. To determine the possible mechanism, NADPH oxidase subunits (Nox-1, Nox-4) mRNA expression, intracellular ROS level, phosphorylation of ERK1/2, NF-kappaB activity, and mRNA expression of AP-1 subunits (c-fos, c-jun) and c-myc were measured. The results demonstrated that reinioside C attenuated Ang II-induced NADPH oxidase mRNA expression, generation of ROS, ERK1/2 phosphorylation, activation of NF-kappaB, and mRNA expression of AP-1 and c-myc in VSMCs in a concentration-dependent manner. The effects of Ang II were also inhibited by diphenyleneiodonium (DPI, the NADPH oxidase inhibitor), PD98059 (the ERK1/2 inhibitor) and pyrrolidine dithiocarbamate (PDTC, the NF-kappaB inhibitor). These results suggest reinioside C attenuates Ang II-induced proliferation of VSMCs by inhibiting NADPH oxidase-ROS-ERK1/2-NF-kappaB-AP-1 pathway.

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.

PyDPI: freely available python package for chemoinformatics, bioinformatics, and chemogenomics studies.

The rapidly increasing amount of publicly available data in biology and chemistry enables researchers to revisit interaction problems by systematic integration and analysis of heterogeneous data. Herein, we developed a comprehensive python package to emphasize the integration of chemoinformatics and bioinformatics into a molecular informatics platform for drug discovery. PyDPI (drug-protein interaction with Python) is a powerful python toolkit for computing commonly used structural and physicochemical features of proteins and peptides from amino acid sequences, molecular descriptors of drug molecules from their topology, and protein-protein interaction and protein-ligand interaction descriptors. It computes 6 protein feature groups composed of 14 features that include 52 descriptor types and 9890 descriptors, 9 drug feature groups composed of 13 descriptor types that include 615 descriptors. In addition, it provides seven types of molecular fingerprint systems for drug molecules, including topological fingerprints, electro-topological state (E-state) fingerprints, MACCS keys, FP4 keys, atom pair fingerprints, topological torsion fingerprints, and Morgan/circular fingerprints. By combining different types of descriptors from drugs and proteins in different ways, interaction descriptors representing protein-protein or drug-protein interactions could be conveniently generated. These computed descriptors can be widely used in various fields relevant to chemoinformatics, bioinformatics, and chemogenomics. PyDPI is freely available via https://sourceforge.net/projects/pydpicao/.

Uncinataflavone, a new flavonoid with a methyl benzoate substituent from Selaginella uncinata.

Uncinataflavone (1), a new flavonoid, together with four known compounds (2-5), was isolated from Selaginella uncinata (Desv.) Spring. Compounds 2 and 3 were isolated from the genus selaginella for the first time. The structure of the new compound was determined as methyl 3-(5,7-dihydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-6-yl)-4-methoxybenzoate by means of spectroscopic evidence, including UV, IR, 1D and 2D NMR analyses as well as HR-ESI-MS. These compounds (1-5) were evaluated for the antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl assay system.

A new flavonoid with 6-phenyl substituent from Selaginella uncinata.

A new flavonoid, 6-(5-acetyl-2-methoxyphenyl)-apigenin (1), together with nine known compounds (2-10), was isolated from Selaginella uncinata (Desv.) Spring. This is the first report of the spectroscopic data of compound 3. Compound 2 was first reported from this species. The structure of the new compound was elucidated on the basis of spectroscopic evidence, including 1D and 2D NMR as well as HR-EI-MS analysis.

Lycopodiastrum casuarinoides: An overview of their phytochemicals, biological activities, structure-activity relationship, biosynthetic pathway and 13C NMR data.

Huperzine A, a lycodine-type alkaloid, exhibits potent inhibitory activity against acetylcholinesterase (AChE) and has been utilized to treat neurodegenerative diseases' symptoms. Lycopodiastrum casuarinoides, a member of the family Lycopodiaceae, is renowned for its lycodine-type alkaloids. Some of these alkaloids show various pharmacological benefits, such as anti-cholinesterase, neuroprotective, and cytotoxic effects. To date, 113 chemical compounds, including seventy-four lycodine-type alkaloids, ten terpenoids, eleven aliphatics, and eighteen other compounds, have been isolated from this plant. In this review, we have discussed phytochemicals and biological activities of the reported compounds of L. casuarinoides. Moreover, structure-activity relationship (SAR), plausible biosynthetic pathways, and 13C nuclear magnetic resonance spectroscopy (13C NMR) data of the lycodine-type alkaloids are also summarized.

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.

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.

Trichocladabiflavone A, a chalcone-flavonone type biflavonoid from Selaginella trichoclada Alsto.

A chalcone-flavonone type biflavonoid, trichocladabiflavone A (1), along with eight known biflavonoids (2-9) were isolated from the 70% EtOH extract of Selaginella trichoclada. Their structures were elucidated by extensive spectroscopic analyses. Compound 1 was the first chalcone-flavonone type biflavonoid reported in the genus Selaginella. Moreover, compound 1 exhibited moderate cytotoxicity against DU145, MCF-7 and PC3 human cancer cell lines.