Machine learning-assisted structure annotation of natural products based on MS and NMR data.

Covering: up to March 2023Machine learning (ML) has emerged as a popular tool for analyzing the structures of natural products (NPs). This review presents a summary of the recent advancements in ML-assisted mass spectrometry (MS) and nuclear magnetic resonance (NMR) data analysis to establish the chemical structures of NPs. First, ML-based MS/MS analyses that rely on library matching are discussed, which involves the utilization of ML algorithms to calculate similarity, predict the MS/MS fragments, and form molecular fingerprint. Then, ML assisted MS/MS structural annotation without library matching is reviewed. Furthermore, the cases of ML algorithms in assisting structural studies of NPs based on NMR are discussed from four perspectives: NMR prediction, functional group identification, structural categorization and quantum chemical calculation. Finally, the review concludes with a discussion of the challenges and the trends associated with the structural establishment of NPs based on ML algorithms.

Structural diversity, hypothetical biosynthesis, chemical synthesis, and biological activity of Ganoderma meroterpenoids.

Covering: 2018 to 2022Meroterpenoids found in fungal species of the genus Ganoderma and known as Ganoderma meroterpenoids (GMs) are substances composed of a 1,2,4-trisubstituted benzene and a polyunsaturated side chain. These substances have attracted the attention of chemists and pharmacologists due to their diverse structures and significant bioactivity. In this review, we present the structures and possible biosynthesis of representative GMs newly found from 2018 to 2022, as well as chemical synthesis and biological activity of some interesting GMs. We propose for the first time a plausible biosynthetic pathway for GMs, which will certainly motivate further research on the biosynthetic pathway in Ganoderma species, as well as on chemical synthesis of GMs as important bioactive compounds for the purpose of drug development.

Development of actein derivatives as potent anti-triple negative breast cancer agents.

Actein is a natural triterpenoid glycoside, isolated from the rhizomes of Cimicifuga foetida, which have been demonstrated to be potential in the treatment of breast cancer previously. Herein, we described the design and synthesis of a series of actein derivatives as anti-triple negative breast cancer (TNBC) inhibitors. Of which, the most promising derivative 27 exhibited significant inhibitory activity against human TNBC cell lines HCC1806 and MDA-MB-231, with IC50 values of 2.78 and 9.11 µM, respectively. Structure-activity relationships of actein derivatives were also discussed. Moreover, preliminary mechanism investigation revealed that 27 significantly inhibited cancer cell proliferation via cell cycle arrest at S phase. In addition, western blot analysis showed that the activation of MAPK signaling pathway might contribute to derivative 27 induced cell death. Overall, these results indicate that 27 has the potential to be developed as a lead compound and compounds with the actein scaffold are a promising novel class of inhibitors to treat TNBC.

Ganoapplins A and B with an unprecedented 6/6/6/5/6-fused pentacyclic skeleton from Ganoderma inhibit Tau pathology through activating autophagy.

Ganoapplins A and B (1 and 2) with a 6/6/6/5/6-fused pentacyclic skeleton containing an aromatic E ring, were obtained from Ganoderma applanatum. Their structures were established through extensive spectroscopic analyses, quantum chemical calculations, including calculated chemical shifts with DP4 + analysis and electronic circular dichroism (ECD). A plausible biosynthetic pathway for 1 and 2 was proposed. Furthermore, their roles in activating autophagy were investigated and the cellular assays showed that 1 and 2 can inhibit tau pathology by inducing autophagy, suggesting their potential against Alzheimer's disease (AD).

Review on factors affecting coffee volatiles: from seed to cup.

The objective of this review is to evaluate the influence of six factors on coffee volatiles. At present, the poor aroma from robusta or low-quality arabica coffee can be significantly improved by advanced technology, and this subject will continue to be further studied. On the other hand, inoculating various starter cultures in green coffee beans has become a popular research direction for promoting coffee aroma and flavor. Several surveys have indicated that shade and altitude can affect the content of coffee aroma precursors and volatile organic compounds (VOCs), which remain to be fully elucidated. The emergence of the new roasting process has greatly enriched the aroma composition of coffee. Cold-brew coffee is one of the most popular trends in coffee extraction currently, and its influence on coffee aroma is worthy of in-depth and detailed study. Omics technology will be one of the most important means to analyze coffee aroma components and their quality formation mechanism. A better understanding of the effect of each parameter on VOCs would assist coffee researchers and producers in the optimal selection of post-harvest parameters that favor the continuous production of flavorful and top-class coffee beans and beverages. © 2021 Society of Chemical Industry.

Functional triterpenoids from medicinal fungi Ganoderma applanatum: A continuous search for antiadipogenic agents.

Previously, we have demonstrated the antiadipogenic benefits of Ganoderma triterpenoids (GTs), which indicated GTs have potential therapeutic implications for obesity. In this study, the EtOAc extract of Ganoderma applanatum was further phytochemically investigated for searching new antiadipogenic agents, which led to the isolation of a total of 15 highly oxygenated lanostane triterpenoids, including 9 new compounds (1-9) and 6 known analogues (10-15). Structurally, ganodapplanoic acids A and B (1, 2) are two rearranged 6/6/5/6-fused lanostane-type triterpenoids with an unusual C-13/C-15 oxygen bridge moiety. In addition, the EtOAc extract (GAE) and isolates (1-4,6-15) were assayed for their antiadipogenic effects in 3T3-L1 adipocytes. The results revealed that compound 9 effectively repressed adipogenesis through down-regulating the expression of major proteins (PPARγ, CEBPß and FAS) involving differentiation and adipogenesis in 3T3-L1 adipocytes. Thus, the present study further demonstrated the antiadipogenic potential of GTs and provided a possible perspective for obesity treatment.

FPR2-based anti-inflammatory and anti-lipogenesis activities of novel meroterpenoid dimers from Ganoderma.

Four pairs of novel meroterpenoid dimers, (±)-applandimeric acids A-D (1-4) with an unprecedented spiro[furo[3,2-b]benzofuran-3,2'-indene] core were isolated from the fruiting bodies of Ganoderma applanatum. Their planar structures were unambiguously determined via extensive spectroscopic analysis. Their relative and absolute configurations were confirmed through calculated internuclear distance, coupling constant, 13C NMR with DP4 + analysis and electronic circular dichroism (ECD). Furthermore, the molecular docking-based method was used to evaluate their interaction with formyl peptide receptor 2 (FPR2) associated with inflammation. Interestingly, (±)-applandimeric acid D (4) can bond with FPR2 by some key hydrogen bonds. Furthermore, an in vitro bioassay verified that 4 can inhibit the expression of FPR2 with IC50 value of 7.93 µM. In addition, compared to the positive control LiCl (20 mM), 4 showed comparable anti-lipogenesis activity at the concentration of 20 µM. Meanwhile, 4 can suppress the protein levels of peroxisome proliferators-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-ß (C/EBP-ß), adipocyte fatty acid-binding protein 4 (FABP4), and fatty acid synthase (FAS) through activating AMP-activated protein kinase (AMPK) signaling pathway. Thus, our findings indicate that compound 4 could be a lead compound to treat obesity and obesity-related diseases by inhibiting lipid accumulation in adipocyte and alleviating inflammation.

Lepipyrrolins A-B, two new dimeric pyrrole 2-carbaldehyde alkaloids from the tubers of Lepidium meyenii.

Nine new pyrrole alkaloids, including two undescribed dimeric pyrrole 2­carbaldehyde alkaloids, lepipyrrolins A-B (1-2), seven pyrrole-alkaloid derivatives, macapyrrolins D-J (3-9), along with three known ones (10-12) were isolated from the rhizomes of Lepidium meyenii. Their structures and absolute configurations were demonstrated by extensive spectroscopic data (1D, 2D NMR, HRESIMS), and calculated electronic circular dichroism (ECD) experiment. Compounds 1, 3-12 were tested for their nitric oxide inhibitory effects. Furthermore, compound 1 was evaluated for its cytotoxic activity against five human tumor cell lines (HL-60, SMMC-7221, A549, MCF-7, and SW480) in vitro, and displayed selective cytotoxicity against SMMC-7721 with IC50 value of 16.78 ± 0.49 µM.

Pyrrolizidine alkaloids from the seeds of Scleropyrum wallichianum.

Two new pyrrolizidine alkaloids, sclerwalins A and B (1 and 2), and one known 9-O-E-hydroxysenecioylretronecine (3) were first isolated from the seeds of Scleropyrum wallichianum. Their chemical structures were elucidated by extensive 1 D NMR and 2 D NMR (HSQC, HMBC, COSY, and ROESY), MS and IR spectra. Cytotoxicities of all isolates were evaluated against five human tumor cell lines (HL-60, A-549, SMMC-7721, MCF-7 and SW480).[Formula: see text].

Macathiohydantoin L, a Novel Thiohydantoin Bearing a Thioxohexahydroimidazo [1,5-a] Pyridine Moiety from Maca (Lepidium meyenii Walp.).

Five new thiohydantoin derivatives (1-5) were isolated from the rhizomes of Lepidium meyenii Walp. NMR (1H and 13C NMR, 1H-1H COSY, HSQC, and HMBC), HRESIMS, and ECD were employed for the structure elucidation of new compounds. Significantly, the structure of compound 1 was the first example of thiohydantoins with thioxohexahydroimidazo [1,5-a] pyridine moiety. Additionally, compounds 2 and 3 possess rare disulfide bonds. Except for compound 4, all isolates were assessed for neuroprotective activities in corticosterone (CORT)-stimulated PC12 cell damage. Among them, compound (-)-3 exhibited moderate neuroprotective activity (cell viability: 68.63%, 20 µM) compared to the positive control desipramine (DIM) (cell viability: 88.49%, 10 µM).

Morphological Changes and Component Characterization of Coffee Silverskin.

Nuclear magnetic resonance (NMR) spectroscopy was used for the qualitative and quantitative analysis of aqueous extracts of unroasted and roasted coffee silverskin (CS). Twenty compounds were identified from 1D and 2D NMR spectra, including caffeine, chlorogenic acid (CGA), trigonelline, fructose, glucose, sucrose, etc. For the first time, the presence of trigonelline was detected in CS. Results of the quantitative analysis showed that the total amount of the main components after roasting was reduced by 45.6% compared with values before roasting. Sugars in the water extracts were the main components in CS, and fructose was the most abundant sugar, its relative content accounting for 38.7% and 38.4% in unroasted and roasted CS, respectively. Moreover, 1D NMR combined with 2D NMR technology shows application prospects in the rapid, non-destructive detection of CS. In addition, it was observed by optical microscopy and scanning electron microscopy (SEM) that the morphology of CS changed obviously before and after roasting.

Meroapplanins A-E: Five Meroterpenoids with a 2,3,4,5-Tetrahydropyridine Motif from Ganoderma applanatum.

Meroapplanins A-E (1-5) with a 2,3,4,5-tetrahydropyridine fragment were isolated from the fruiting bodies of Ganoderma applanatum. Their structures were elucidated by comprehensive spectroscopic analyses. Their absolute configurations were established based on the X-ray diffraction, electronic circular dichroism (ECD), and calculated nuclear magnetic resonance (NMR) with DP4+ analysis. A plausible biosynthetic pathway for 1-5 was proposed. Furthermore, compounds 1-5, together with optically pure compounds 1a-4a and 1b-4b, were evaluated for their protective effects in PC12 cells damaged by H2O2. The results showed that 3b had protective activity with a cell viability of 82.58 ± 1.31%, compared with the model group (cell viability: 65.27 ± 1.48%).

Highly oxygenated lanostane triterpenoids from Ganoderma applanatum as a class of agents for inhibiting lipid accumulation in adipocytes.

Ganoderma triterpenoids (GTs), a class of major active constituents in Ganoderma species, play an important role in the anti-obesity effect of Ganoderma fungi. In the study, seventeen new highly oxygenated lanostane triterpenoids, ganoapplanoids A-Q (1-17), together with five previously reported compounds (18-22), were isolated from the fruiting bodies of Ganoderma applanatum. Their structures were confirmed by comprehensive spectroscopic analyses, single-crystal X-ray diffraction and Mo2(OAc)4 induced CD cotton effect. Structurally, compound 6 represents the first example of 2-norlanostane triterpenoid possessing an unusual semiacetal moiety. Furthermore, isolates (1-5, 7-11, 13-22, 3a) were evaluated for regulatory effects on lipid accumulation by 3T3-L1 adipocytes model. Among them, compounds 11 and 17 exhibited significant potency in blunted adipogenesis activities dose-dependently. Meanwhile, compounds 11 and 17 reduced triglyceride (TG) and total cholesterol (TC) levels in the adipocytes. These results supported that the highly oxygenated lanostane triterpenoids from G. applanatum may serve as agents for inhibiting the lipid accumulation in adipocytes and the G. applanatum provided an important source for searching new drugs to treat obesity.

Isolation of benzolactones, Ganodumones A-F from Ganoderma lucidum and their antibacterial activities.

Six previously undescribed benzolactone constituents, ganodumones A-F (1-6), a new type of Ganoderma meroterpenoids (GMs) fused with 1,2,3,4,5-pentasubstituted phenyl and 1',2'-dioxy-3'-methyl-pentyl chain were isolated from the fruiting bodies of Ganoderma lucidum. Their structures were determined by spectroscopic analysis, X-ray crystal diffraction, and ECD computational methods. Meanwhile, bioactive evaluation showed that compounds 3 and 5 have antibacterial activities against Microsporum gypseum with MIC90 56.86 ± 3.98 and 18.48 ± 0.47 µg/mL, respectively.

Structurally diverse lanostane triterpenoids from medicinal and edible mushroom Ganoderma resinaceum Boud.

Ganoderma resinaceum is a multi-purpose herbal medicine that is homologous to functional food that has long been used for enhancing health and treating chronic hepatopathy in Traditional Chinese Medicine. In a search program to discover the key bioactive composition of G. resinaceum, sixteen new lanostane-type triterpenoids (1-16), and twenty known analogues (17-36) were isolated from the fruiting bodies of G. resinaceum. Spectroscopic analyses and X-ray crystallography were used to determine the new structures. Furthermore, the spectroscopic properties of 15ß-hydroxy-4,4,14α- trimethyl-3,7,11,20-tetraoxo-5α-pregn-8-ene (15) and 15α-hydroxy-4,4,14α-trimethyl- 3,7,11,20-tetraoxo-5α-pregn-8-ene (34) indicated a potential structural misassignment of their analogues, lucidone E and lucidone H, reported previously. To probe this hypothesis, ROESY experiments and single-crystal X-ray diffraction analysis were conducted. These results undoubtedly reassigned the structure of lucidone E and lucidone H. Biological evaluation of the selected compounds disclosed that compounds 3, 4, 7/21, 11, 12, 13/14, 17, 18, 24/25, 27, 30, 31, and 35 had significant hepatoprotective activities, due to their remarkable in vitro inhibitory activities against the increase of ALT and AST levels in HepG2 cells induced by H2O2.

Cytotoxic Limonoids from the Twigs and Leaves of Toona ciliata.

Eight new limonoids, toononoids A-H (1-8), eight new B-seco-29-norlimonoids, toonanoronoids A-H (9-16), and seven known analogues were obtained from the EtOAc extract of the twigs and leaves of Toona ciliata. Compounds 2, 4, 8, and 16 are rare lactam-bearing limonoids. Compounds 1, 14, and 15 possess an unusual γ-methoxybutenolide moiety at C-17, while compounds 9, 10, and 15 have a rare 3ß-hydroxy group. Their 2D structure and relative configurations were identified using spectroscopic data. The absolute configurations of 1, 9, 14, and 15 were established via X-ray diffraction crystallography or comparison of experimental and calculated ECD data. The cytotoxicity of the compounds was assessed toward five human tumor cell lines, and their anti-inflammatory activity was assessed based on NO production using LPS-stimulated RAW264.7 macrophages. Compounds 11 and 12 exerted inhibition toward two tumor cell lines (MCF-7, SW-480) with IC50 values between 2.1 and 3.7 µM, while 18-22 inhibited the proliferation of HL-60, MCF-7, and SW-480 cells (IC50 0.6-4.0 µM). Only compound 4 exhibited weak anti-inflammatory activity with an IC50 value of 28.3 µM.

New Cytotoxic Cycloartane Triterpenes from the Aerial Parts of Actaea heracleifolia (syn. Cimicifuga heracleifolia).

One new 15,16-seco-cycloartane triterpene (1: ), three new cycloartane triterpene glycosides (2: -4: ), and five known compounds (5: -9: ) were isolated from the aerial parts of Actaea heracleifolia. The chemical structures of these compounds were determined on the basis of NMR analysis, HRTOF-ESIMS data, and other spectroscopic methods. Selected compounds were evaluated for their cytotoxicity against human tumor cell lines (HL-60, SMMC-7721, A549, MCF-7, and SW480) in vitro. Compounds 3: and 4: showed weak activity against the HL-60, A-549, and MCF-7 cell lines with IC50 values ranging from 21.34 to 36.98 µM.

A new indole alkaloid from Cimicifuga heracleifolia.

A new alkaloid, (E)-3-(3-methyl-1-oxo-2-butenyl)-6-methoxy-1 H -indole (1), along with two known ones, was isolated from the aerial parts of Cimicifuga heracleifolia. The structure of 1 was elucidated on the basis of extensive spectroscopic data analysis. The structures of known compounds were determined by comparison with the literature data.

Physalis peruviana-Derived 4ß-Hydroxywithanolide E, a Novel Antagonist of Wnt Signaling, Inhibits Colorectal Cancer In Vitro and In Vivo.

Deregulation of the Wnt signaling pathway leads to colorectal cancer progression. Natural dietary compounds serve as promising candidates for development as chemopreventive agents by suppressing the Wnt/ß-catenin signaling pathway. Physalis peruviana-derived 4ßHWE showed a significant inhibitory activity with a calculated IC50 of 0.09 µΜ in a screening of novel inhibitors of Wnt signaling with the dual-luciferase reporter assay. This study investigated the anti-tumor effect of 4ßHWE and the potential Wnt signaling inhibitory mechanism. Both the western blot analysis and immunofluorescence assay showed that 4ßHWE promoted the phosphorylation and degradation of ß-catenin and the subsequent inhibition of its nuclear translocation to attenuate the endogenous Wnt target gene expression in colorectal cancer (CRC) cells. The cell viability assay indicated that 4ßHWE preferentially inhibited the proliferation of CRC compared with CCD-841-CoN, a normal human colonic epithelial cell line. 4ßHWE-mediated G0/G1 cell cycle arrest and apoptosis induction contributed to the suppression of the proliferation of CRC in the cell cycle and Annexin V-FITC/Propidium Iodide apoptosis analysis. Moreover, in vivo, 4ßHWE dramatically inhibited tumor growth in HCT116 xenografts by attenuating the Wnt/ß-catenin signaling pathway. In conclusion, our study suggested that 4ßHWE could be of potential use in anti-tumor agent development as a novel Wnt signaling inhibitor.

Ganolearic Acid A, a Hexanorlanostane Triterpenoid with a 3/5/6/5-Fused Tetracyclic Skeleton from Ganoderma cochlear.

Ganolearic acid A (1), a 3,4- seco-hexanortriterpenoid featuring a rare 3/5/6/5 tetracyclic system, was obtained in trace amounts from Ganoderma cochlear by a LC-UV/MS-guided method. Meanwhile, a new 3,4- seco-nortriterpenoid, fornicatin M (2), as well as its biogenetic precursor, fornicatin D (3), was isolated. The stereochemical structure of 1 was completely established by 1D, 2D NMR, IR, and HRMS spectra, as well as 13C NMR and electronic circular dichroism calculations. The plausible biogenetic pathway of 1 and 2 was proposed. Furthermore, their anti-inflammatory activities were evaluated.