2D NMR Spectroscopy Research Articles

Revisiting the Cyclocephagenols via Astragalus condensatus: Structural Insights and Configurational Revision.

The phytochemical investigation of the MeOH extract of Astragalus condensatus roots led to the discovery of a new tetrahydropyran cycloartane-type triterpenoid, astracondensatol A (1), alongside six known cyclocephagenol derivatives (2, 3, 20, 32, 35, and 36). Elucidation of their structures involved 1D and 2D-NMR spectroscopy and mass data analysis. Upon comparing NMR spectroscopic data with prior literature, several carbon shift anomalies, particularly at C-24, prompted a reevaluation using quantum chemical calculations, resulting in the revision of the 24S to 24R absolute configuration for compound 2 and 38 other reported cyclocephagenol-type triterpenoids. X-ray crystallography data further supported the analysis in establishing the absolute configuration of compound 2. Ambiguous NOE correlations and publication bias could have played a significant role in miss-assigning the C-24 absolute configuration in tetrahydropyran cycloartane-type triterpenoids.

Mapping Natural Sugars Metabolism in Acute Myeloid Leukaemia Using 2D Nuclear Magnetic Resonance Spectroscopy

Metabolism plays a central role in cancer progression. Rewiring glucose metabolism is essential for fulfilling the high energy and biosynthetic demands as well as for the development of drug resistance. Nevertheless, the role of other diet-abundant natural sugars is not fully understood. In this study, we performed a comprehensive 2D NMR spectroscopy tracer-based assay with a panel of 13C-labelled sugars (glucose, fructose, galactose, mannose and xylose). We assigned over 100 NMR signals from metabolites derived from each sugar and mapped them to metabolic pathways, uncovering two novel findings. First, we demonstrated that mannose has a semi-identical metabolic profile to that of glucose with similar label incorporation patterns. Second, next to the known role of fructose in driving one-carbon metabolism, we explained the equally important contribution of galactose to this pathway. Interestingly, we demonstrated that cells growing with either fructose or galactose became less sensitive to certain one-carbon metabolism inhibitors such as 5-Flurouracil and SHIN1. In summary, this study presents the differential metabolism of natural sugars, demonstrating that mannose has a comparable profile to that of glucose. Conversely, galactose and fructose contribute to a greater extent to one-carbon metabolism, which makes them important modulators for inhibitors targeting this pathway. To our knowledge, this is the first NMR study to comprehensively investigate the metabolism of key natural sugars in AML and cancer.

Synthesis of Sulfonamide-Based Schiff Bases as Potent Anticancer Agents: Spectral Analyses, Biological Activity, Molecular Docking, ADME, DFT, and Pharmacophore Modelling Studies.

The current study focuses on the synthesis and characterization of six benzenesulfonamide-based Schiff base derivatives (7-12) with various electron-withdrawing and electron-donating substituents (-F, -CI, -Br, -CH3, and -OCH3) and the assessment of their antiproliferative activities against human lung (A549) and liver (HepG2) cancer cell lines using in vitro and in silico approaches. The structures of the synthesized compounds (7-12) were elucidated by elemental analysis and FT-IR, 1D (1H, 13C, APT, and DEPT-135), and 2D (HMQC and HMBC) NMR spectroscopies. The cytotoxic activities of the targeted compounds were determined at various concentrations against these cancer cell lines for 72 h, using the MTT method. The targeted molecules (7-12) demonstrated remarkable antiproliferative activities, with IC50 values ranging from 6.032-9.533 μM against the A549 cell line and 5.244-9.629 μM against the HepG2 cell line. These compounds showed activities at lower or very similar concentrations to cisplatin against the A549 cell line and at much lower concentrations than cisplatin against the HepG2 cell line. Among them, compounds 10 and 12 were found to be more effective against A549 and HepG2 cells, respectively, than cisplatin. These compounds were analyzed by interacting with the 1BNA, 4HJO, and 4ASD crystal structures in molecular docking studies.

Water-Soluble Curcumin Derivatives Including Aza-Crown Ether Macrocycles as Enhancers of their Cytotoxic Activity.

The synthesis of three novel curcumin derivative compounds, featuring aza-crown ether macrocycles of various sizes (aza-12-crown-4, aza-15-crown-5, and aza-18-crown-6), is described. The incorporation of these aza-crown macrocycles significantly enhances their water solubility, positioning them as groundbreaking instances of curcumin derivatives that are fully soluble in aqueous environments. These curcumin ligands (L1, L2, and L3) were then reacted with zinc acetate to afford the coordination metal complexes (L1-Zn, L2-Zn, and L3-Zn). Comprehensive characterization of all compounds was achieved using various analytical techniques, including 1D and 2D NMR spectroscopy, ATR-FTIR spectroscopy, mass spectrometry (ESI+), elemental analysis and UV-Vis spectroscopy. The in vitro cytotoxic activity of both, ligands and complexes were evaluated on three human cancer cell lines (U-251, MCF-7, and SK-LU-1). Compared to conventional curcumin, these compounds demonstrated improved antiproliferative potential. Additionally, a wound healing assay was conducted to assess their antimigration properties. The obtained results suggest that these modifications to the curcumin structure represent a promising approach for developing therapeutic agents with enhanced cytotoxic properties.

Melt Polycondensation Strategy to Access Unexplored l-Amino Acid and Sugar Copolymers.

Biodegradable polymers from bioresources are highly in demand for the development of sustainable polymer platforms for commodity plastics and in the biomedical field. Here, an elegant one-pot synthetic strategy is developed, for the first time, to access unexplored hybrid polymers from two naturally abundant resources: carbohydrates (sugars) and l-amino acids. A bottleneck in the synthetic strategy is overcome by tailor-making d-mannitol-based six- and five-membered bicyclic acetalized diols, and their structures are confirmed by single-crystal X-ray diffraction and 2D NMR spectroscopy. l-Amino acids are converted into ester-urethane functional monomers, and they are polymerized with sugar-diols under solvent-free melt polycondensation to yield biodegradable poly(ester-urethane)s. Acid-catalyzed deprotection yielded amphiphilic polymers having exclusively alternating residues of sugar and l-amino acid in the polymer backbone. The polymer is self-assembled into 200 ± 10 nm sized nanoparticles that can encapsulate fluorescent dyes, are nontoxic to cells up to 250 μg/mL, and are readily endocytosed for lysosomal enzymatic biodegradation at the cellular level.

Modular Synthesis of Monoanionic PN Ligands Leads to Unexpected Structural Diversity in Lanthanum Chemistry.

We report a new synthetic entry to a series of N-substituted anilidophosphine ligands (short HPNR, R = pTol (HPNTol), 3,5-dimethylphenyl (HPN3,5Me), 3,5-bis(trifluoromethyl)phenyl (HPN3,5CF3), 2-methoxyphenyl (HPNOMe), diisopropylphenyl (HPNDipp), and adamantyl (HPNAd)), allowing a detailed tuning of their steric (and electronic) properties. HPNR could be converted into their lithium salts LiPNR, which are effective precursors for salt metathesis reactions. The new ligands are used for the synthesis of an array of lanthanide complexes using LaCl3(THF)1.2 as a precursor. Depending on the steric bulk of the anilidophosphine ligand, either chloride-bridged dimers of the general formula [(PNR)2La(μ-Cl2)La(PNR)2] (R = pTol (3f), 3,5-dimethylphenyl (3d) and adamantyl (3a)) or mononuclear complexes of the general formula (PNR)2LaCl (R = diisopropylphenyl (3e)) are observed, if the complexation reaction is carried out in toluene. Contrary, if salt metathesis reactions are carried out in dimethoxyethane (DME) as a coordinating solvent, -ate complexes of the general formula [(PNR)2La(μ-Cl2)Li(DME)] (R = Adamantyl (4a) and R = 2-methoxyphenyl (4d)) or [Li(DME)3][(PNR)2LaCl2] (R = 3,5-bis(trifluoromethyl)phenyl (4b), R = pTol (4f) and R = 3,5-dimethylphenyl (4d)) are observed. All ligands and complexes have been thoroughly characterized by 1D and 2D NMR spectroscopy, IR, and X-ray crystallography. Finally, the steric demand of the new anilidophosphine ligands is evaluated using SambVca simulations.

Intrinsically Flame‐Retardant Polyamide 6 by Anionic Ring‐Opening Copolymerization with a Phosphorous‐Containing Comonomer

AbstractA three‐step synthetic route is established for the synthesis of a phosphorus‐containing ε‐caprolactam derivative, starting from cyclohex‐2‐enone and diphenylphosphinous chloride, followed by a Beckmann rearrangement. 2D NMR spectroscopy reveals that the phosphorus moiety is selectively localized at the 4‐position of the caprolactam ring. Different amounts of the phosphorus‐containing comonomer are systematically incorporated into polyamide 6 by anionic ring‐opening copolymerization with ε‐caprolactam at elevated temperatures. Polymerization reactions are initiated by a latent, CO2 protected N‐heterocyclic carbene in the presence of N‐acetyl caprolactam and MgCl2. The phosphorus content is determined by inductively‐coupled plasma‐optical emission spectroscopy (ICP‐OES) analysis. Limiting oxygen indices up to 23.5 are found for polymers containing ≈1 wt.‐% of phosphorus. The thermal properties of the copolymers are determined and compared to those of polyamide 6.

Structural characterization of arabinogalactan-II and pectin from Urtica cannabina

Comparative analysis of extracellular and cell wall glycans from Urtica cannabina leaves was performed using chemical methods, GC, GC–MS, 1D, and 2D NMR spectroscopy. The structures of extracellular AG-II and cell wall AG-II are similar. The units are typical for AG-IIs: β-GlcpA-4-OMe-(1→, Rhap-(1 → 4)-β-GlcpA-(1→, attached to β-Galp at O-6, as well as arabinan chains attached to β-Galp at O-3. A single Araf and a trisaccharide formed by 2,5-Araf and two terminal Araf form short arabinan side chains in AG-II. 1,5-arabinan with a backbone substituted by a single Araf at O-3 was identified only in the side chains of cell wall AG-II. The side chains can be attached to O-3 and O-6 of the same β-Galp to form a bifurcated AG side chain. The backbone of AG-II is formed by 1,6- rather than 1,3-linked Galp, although it does include some 1,3-Galp. The high content of 3,6-Galp shows the highly branched nature of the AG carbohydrate chains. From the cell wall, AGP was extracted together with pectin, the simultaneous elution of which from both DEAE-cellulose and Sepharose may indicate a link between them.

Cyclic carbamates based on (R)-(+)-limonene oxide for ring-opening polymerization

A novel synthetic pathway for synthesizing isocyanate-free polyurethanes is reported here. β-Amino alcohols were efficiently synthesized from the aminolysis of the epoxide ring of (R)-(+)-limonene oxide with different primary amines as nucleophiles and hot water as catalysts. The regio- and diastereoselectivities of the reactions were investigated and supported by computational studies. DFT calculations were performed to understand the experimental results more deeply. It confirmed the crucial roles of water molecules and the nature of the nucleophile in forming the products. The formation of the product is entirely driven by the free energy of activation that affects the reaction rate. Cyclic carbamates were prepared from β-amino alcohols using the dialkyl carbonate (DAC) chemistry. An oligourethane was obtained from Anionic Ring-Opening Polymerization (AROP) of a cyclic carbamate derived from (R)-(+)-limonene-oxide. All the products were characterized by employing 1H and 13C NMR spectroscopies. The assignments of the signals in 1H and 13C NMR spectra were also supported by 2D NMR spectroscopy.

New acid anhydride from Phalaris canariensis with antimicrobial activity assessed through in vitro and in silico approaches

In this study, a novel fatty acid anhydride, named phalarisin 1, was successfully isolated from the ethyl acetate extract of Phalaris canariensis growing in Tunisia. The structural characterisation of the compound was achieved through various spectroscopic techniques including FT-IR, 1D and 2D-NMR spectroscopy, as well as acidic hydrolysis analyses. Remarkably, phalarisin exhibited potent antimicrobial properties against a range of pathogens including Micrococcus luteus, Bacillus subtilis, Fusarium oxysporum, and Fusarium phylophylum, with minimum inhibitory concentrations (MICs) ranging from 31.25 to 62.5 μg/mL. To grasp the antimicrobial potential of compound 1, molecular docking studies were performed and they furnished evidence indicating its ability to bind to proteins in bacteria and fungi that are pivotal for drug resistance.

Acyclic Diaminocarbene Platinum(IV) Complexes Synthesized by the Oxidative Addition of MeI and I<sub>2</sub>

The oxidative addition of methyl iodide or molecular iodine to the bis(С,N-chelate) deprotonated diaminocarbene platinum(II) complexes [Pt{C(N(H)Ar)(NC(N(H)Ph)N(Ph)}2] (Ar = C6H3-2,6-Me2 (Xyl), C6H2-2,4,6-Me3 (Mes), and C6H4-4-Me (pTol)) affords the corresponding platinum(IV) derivatives in a yield of 89–99%. The addition of CF3CO2H is accompanied by the protonation of the nitrogen atoms of the diaminocarbene fragment to form the cationic complexes [[PtI(X)-{C(N(H)Ar)(NC(N(H)Ph)N(Ph)}2]CF3CO2H (X = Me, I). The structures of the compounds are determined by elemental analysis; high resolution mass spectrometry with electrospray ionization (ESI HRMS); IR spectroscopy; 1H, 13C{1H}, 19F{1H}, and 195Pt{1H} NMR spectroscopy; 2D NMR spectroscopy (1H,1Н COSY, 1H,1Н NOESY, 1H,13C HSQC, 1H,13C HMBC, 1H,15N HSQC, 1H,15N HMBC), and X-ray diffraction (XRD) and thermogravimetric analyses. The synthesized platinum(IV) complexes are thermally stable to 200–260°C and are electroneutral molecules with the octahedral coordination sphere formed by two deprotonated diaminocarbene C,N-chelate substituents and iodine and methyl or two iodine atoms localized in the apical positions.

Chemical structures of polyketides and alkaloids isolated from a culture of fungus Curvularia moringae

Seven new polyketides [moringols I–VII (1–7)], a new alkaloid [moringamine I (8)], and seven known compounds (9–15) were isolated from the fungus Curvularia moringae JKYM-KR4. The planar chemical structures and relative configurations of the new compounds were elucidated by high-resolution mass spectrometry, 1D and 2D NMR spectroscopy, and DP4+ analysis using the calculated 13C NMR chemical shifts. For moringols I and II (1 and 2), the planar chemical structures and relative configurations were confirmed using X-ray crystallography. The absolute configurations of 1–6 and 8 were determined by ECD calculations. Among the isolated compounds, terpestacin (14) moderately inhibited the proliferation of HT-29 cells.

“Novel chemo-enzymatic synthesis, structural elucidation and first antiprotozoal activity profiling of the atropoisomeric dimers of trans-8-Hydroxycalamenene”

Leishmaniasis and malaria are two debilitating protozoan diseases affecting millions globally, particularly in tropical and subtropical regions. Current therapeutic options face significant challenges due to emerging drug-resistant strains, necessitating the discovery of novel antiprotozoal agents. This study explores, for the first time, the antiprotozoal potential of calamenenes and their dimers, naturally occurring sesquiterpenes found in essential oils, through a novel chemo-enzymatic synthesis approach. Using the laccase from Trametes versicolor, atropoisomeric dimers of (−)- and (+)-8-trans-hydroxycalamenene were synthesized from commercially available (−)- and (+)-menthol. Structural elucidation was achieved via 2D-NMR spectroscopy, electronic circular dichroism, and DFT calculations. In vitro profiling against Leishmania spp and drug-resistant Plasmodium falciparum revealed that calamenene dimers exhibited significantly higher antiprotozoal activity compared to their monomeric counterparts, highlighting the potential of dimeric terpenoids as promising antiprotozoal agents. This work lays the foundation for developing novel antimalarial drugs based on calamenene scaffolds, encouraging further interactome studies to optimize their pharmacological properties.

Bioassay Guided Isolation and α-Glucosidase Inhibition Studies of a New Sesquiterpene from Ochradenus aucheri.

The aim of the current study was to explore the anti-diabetic potential of Ochradenus aucheri Boiss (O. aucheri). All the fractions of O. aucheri were evaluated for α-glucosidase inhibition, followed by bioassay-guided isolation which resulted in a new sesquiterpenoid, as a potential α-glucosidase inhibitor. The preliminary screening showed that all the fractions including n-hexane (38.0 ± 1.38 μg/mL), dichloromethane (92.6 ± 6.18 μg/mL), ethyl acetate (29.2 ± 0.51 μg/mL) and n-butanol (361.8 ± 5.80 μg/mL) displayed significant α-glucosidase inhibitory activity. The activity-directed fractionation and purification of ethyl acetate fraction led to the isolation of one new sesquiterpenoid, Jardenol (1), and two known metabolites: β-stitosterol-3-O-β-D-glucopyranoside (2) and β-Sitosterol (3). To the best of our knowledge, these metabolites have not been isolated from this plant previously. The structure of the new metabolite 1 was confirmed through 1D and 2D NMR spectroscopy, and MS analysis. Compound 1 showed significant α-glucosidase inhibition with an IC50 value of 138.2 ± 2.43 μg/mL as compared to positive control acarbose (IC50 = 942.0 ± 0.60 μg/mL). Additionally, in-silico docking was employed to predict the binding mechanism of compound 1 in the active site of the target enzyme, α-glucosidase. The docking results suggested that the compound forms strong interactions at the catalytic site of α-glucosidase. The results of the present study indicated that the newly purified secondary metabolite, Jardenol, can be a promising anti-diabetic compound.

Sesquiterpene Coumarins, Chromones, and Acetophenone Derivatives with Selective Cytotoxicities from the Roots of Ferula caspica M. Bieb. (Apiaceae).

In search of selective cytotoxic compounds from Ferula species as potential leads for the treatment of various cancer diseases, a bioactivity-guided isolation study was performed on the roots of Ferula caspica M. Bieb. COLO 205 (colon), K-562 (leukemia), and MCF-7 (breast) cancer cell lines were used to monitor the cytotoxic activity of column fractions and determine the IC50 value of the active compounds. In addition to the seven known (5-11) compounds, four previously unknown compounds: kayserin A (1), kayserin B (2), 8'-epi-kayserin B angelate (3), and 3-epi-ferulin D (4) were isolated from the dichloromethane extract of the roots of F. caspica. Structure elucidation of the isolated compounds was carried out by extensive spectroscopic analyses such as 1D- and 2D-NMR spectroscopy, High-Resolution Mass Spectroscopy (HRMS), IR spectroscopy, and UV spectroscopy. Although all of the isolated compounds showed various degrees of cytotoxic activity on COLO 205, K-562, and MCF-7 cancer cell lines, the most potent compounds were identified in the following order: 1-Hydroxy-1-(1'-farnesyl)-4,6-dihydroxyacetophenone (HFDHAP, 11), 3-epi-ferulin D (3EFD, 4), and 7-desmethylferulin D (7DMFD, 6). The cytotoxic activities of all three compounds were more potent than that of the reference compound cisplatin (Cis) against all tested cancer cell lines. Still, only HFDHAP (11) was more potent than the reference compound doxorubicin (Dox) against the MCF-7 cancer cell line. The mechanism of action of these three compounds was investigated on the COLO 205 cell line. The results indicated that compounds 4, 6, and 11 trigger caspase-3/8/9 activation and suppress the anti-apoptotic protein, Bcl-xL. Molecular docking studies confirmed the interactions of the three cytotoxic molecules with the active site of the Bcl-xL protein.

Synthesis, spectroscopic characterization, DFT calculations, in silico-ADMET and molecular docking analysis of novel quinoline-substituted 5H-chromeno [2,3-b] pyridine derivatives as antibacterial agents.

A convenient, straightforward, and effective one-step reaction for the synthesis of a three-component compound of biologically relevant novel 2,4-diamino-5-(8-hydroxyquinolin-7-yl)-5H-chromeno[2,3-b] pyridine-3-carbonitrile derivatives was designed and synthesized. The synthesis was developed by the reaction between salicylaldehyde 1, 8-hydroxyquinoline 2, 2-aminopropene-1,1,3-tricarbonitrile 3, and the catalytic amount of triethylamine in ethanol at 78°C. This methodology has many beneficial features, including the use of inexpensive and non-hazardous starting materials, single-flask reactions, optimized reaction conditions, the termination of intermediate isolation, easy workup, reducing organic waste products, being chromatography-free, and decreasing the reaction time along with quantitative yields with high functional group tolerance. A proposed mechanism with supporting experimental data is presented, including 1H NMR, 13C NMR, 2D NMR (HMBC, COSY, HSQC), mass, and IR spectroscopy, which are used to characterize the complete derivatives. All synthesized compounds were evaluated in vitro for their antibacterial activities against Bacillussubtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa bacterial strains via the agar-well diffusion method compared with the reference drug gentamicin. The data indicated that compounds 4A, 4F, 4G, 4J, and 4K consistently demonstrated strong antimicrobial activity against Gram-positive and Gram-negative bacteria. Furthermore, a molecular docking investigation was carried out to gain insight into the binding mode of the most promising compounds via the crystal structure of the S. aureus DNA gyrase complex with ciprofloxacin (PDB ID: 2XCT). Density functional theory (DFT) calculations were performed to determine the various molecular properties of the synthesized novel 2,4-diamino-5-(8-hydroxyquinolin-7-yl)-5H-chromeno [2,3-b] pyridine-3-carbonitrile derivatives (4A-4M). On the basis of the reactive sites explored by the molecular electrostatic potential maps, the antibacterial activities of the compounds were screened.

P‐Terphenyl and Orsellinic Acid Derivatives from the European Polyporales Terana coerulea and Sparassis brevipes

Investigation of the secondary metabolites of the solid‐state rice cultures from the European basidiomycetes Terana coerulea and Sparassis brevipes afforded three previously undescribed secondary metabolites identified as two p‐terphenyl derivatives (1 and 2) and one orsellinic acid congener (3) in addition to another known, isoeverninic acid (4). Chemical structures of the isolated compounds were elucidated through comprehensive 1D and 2D NMR spectroscopic analyses, coupled with HR‐MS and other spectral methods. The isolated compounds were assessed for their cytotoxic and antimicrobial activities. Compound 1 revealed weak antimicrobial properties, whereas the inseparable mixture of 3 and 4 featured moderate cytotoxic and antimicrobial effects.

Deciphering fucosylated protein-linked O-glycans in oral Tannerella serpentiformis: insights from NMR spectroscopy and glycoproteomics

Abstract Tannerella serpentiformis is a health-associated Gram-negative oral anaerobe, while its closest phylogenetic relative is the periodontal pathogen Tannerella forsythia. The pathogen employs glycan mimicry through protein O-glycosylation, displaying a terminal nonulosonic acid aiding in evasion of host immune recognition. Like T. forsythia, T. serpentiformis cells are covered with a 2D-crystalline S-layer composed of two abundant S-layer glycoproteins-TssA and TssB. In this study, we elucidated the structure of the O-linked glycans of T. serpentiformis using 1D and 2D NMR spectroscopy analyzing S-layer glycopeptides and β-eliminated glycans. We found that T. serpentiformis produces two highly fucosylated, branched glycoforms carrying non-carbohydrate modifications, with the structure [2-OMe-Fuc-(α1,2)]-4-OMe-Glc-(β1,3)-[Fuc-(α1,4)]-2-NAc-GlcA-(β1,4)-[3-NH2, 2,4-OMe-Fuc-(α1,3)]-Fuc-(α1,4)-Xyl-(β1,4)-[3-OMe-Fuc-(α1,3)]-GlcA-(α1,2)-[Rha-(α1,4]-Gal, where the 3OMe-Fuc is variable; each glycoform contains a rare 2,4-methoxy, 3-amino-modified fucose. These glycoforms support the hypothesis that nonulosonic acid is a hallmark of pathogenic Tannerella species. A combined glycoproteomics and bioinformatics approach identified multiple sites within TssA (14 sites) and TssB (21 sites) to be O-glycosylated. LC–MS/MS confirmed the presence of the Bacteroidetes O-glycosylation motif (D)(S/T) (L/V/T/A/I) in Tannerella species, including the newly identified candidate “N” for the third position. Alphfold2 models of the S-layer glycoproteins were created revealing an almost uniform spatial distribution of the two glycoforms at the N-terminal two thirds of the proteins supported by glycoproteomics, with glycans facing outward. Glycoproteomics identified 921 unique glycopeptide sequences corresponding to 303 unique UniProt IDs. GO-term enrichment analysis versus the entire T. serpentiformis proteome classified these proteins as mainly membrane and cell periphery-associated glycoproteins, supporting a general protein O-glycosylation system in T. serpentiformis.

Discovery of Coumarins from Zanthoxylum dimorphophyllum var. spinifoliumas and Their Potential against Rheumatoid Arthritis.

In the present study, a series of coumarins, including eight undescribed bis-isoprenylated ones Spinifoliumin A-H, were isolated and identified from the aerial parts of Zanthoxylum dimorphophyllum var. spinifolium (ZDS), a plant revered in traditional Chinese medicine, particularly for treating rheumatoid arthritis (RA). The structures of the compounds were elucidated using 1D and 2D NMR spectroscopy, complemented by ECD, [Rh2(OCOCF3)4]-induced ECD, Mo2(OAc)4 induced ECD, IR, and HR-ESI-MS mass spectrometry. A network pharmacology approach allowed for predicting their anti-RA mechanisms and identifying the MAPK and PI3K-Akt signaling pathways, with EGFR as a critical gene target. A CCK-8 method was used to evaluate the inhibition activities on HFLS-RA cells of these compounds. The results demonstrated that Spinifoliumin A, B, and D-H are effective at preventing the abnormal proliferation of LPS-induced HFLS-RA cells. The results showed that compounds Spinifoliumin A, D, and G can significantly suppress the levels of IL-1β, IL-6, and TNF-α. Moreover, molecular docking methods were utilized to confirm the high affinity between Spinifoliumin A, D, and G and EGFR, SRC, and JUN, which were consistent with the results of network pharmacology. This study provides basic scientific evidence to support ZDS's traditional use and potential clinical application.

Highly oxygenated antiplasmodial and non-hemolytic Δ7,9(11) stigmastane-type steroids from the twigs of Vernonia amygdalina Delile

Chemical investigations of a methanolic extract of the twigs of Vernonia amygdalina Delile (Asteraceae) resulted in the isolation and identification of three previously undescribed highly oxygenated Δ7,9(11) stigmastane-type steroids namely vernonins U−W (1−3) along with six known compounds (4−9). The structural characterization of all the isolated compounds has been conducted via comprehensive 1D- and 2D-NMR spectroscopy as well as HRMS. The seven steroidal derivatives 1−7 were evaluated for their antiplasmodial activity against the chloroquine-resistant strain P. falciparum Dd2 (PfDd2) and their hemolytic effect on human red blood cells (RBCs). Vernonins U (1), A (4) and stigmasterol-3-O-β-D-glucopyranoside (7) showed the highest activity with IC50 values of (5.47 ± 0.01) μg/mL, (6.02 ± 0.13) μg/mL and (6.34 ± 0.80) μg/mL, respectively, against PfDd2, while vernonin W (3) showed moderate activity of (21.20 ± 0.40) μg/mL. None of the tested compounds displayed hemolytic effects on human RBCs up to 100 μg/mL indicating their safety. These results enrich the known chemistry of V. amygdalina and support its use in folk medicine for the treatment of malaria. This encourages further research towards new antiplasmodial drug candidates from this plant.