In an endeavor to discover natural product-derived novel green herbicides, twenty-three new anethole-based 4-methyl-1,2,4-triazole-thioether compounds were synthesized, and their chemical structures were confirmed by various approaches, including Fourier transform infrared (FT-IR) spectroscopy, 1H/13C-nuclear magnetic resonance (NMR) spectroscopy, and atmospheric pressure chemical ionization-high resolution mass spectrometry (APCI-HRMS). The selective mechanism of the nucleophilic substitution in the reaction process of the intermediate 5 was investigated through natural bond orbital (NBO) analysis. The herbicidal activity of the target compounds was evaluated, and compound 6c demonstrated good herbicidal effect against the dicotyledonous plant Brassica campestris as well as a certain degree of broad-spectrum activity against the two tested weeds. The EC50 value demonstrated that compound 6c exhibited superior inhibitory activity against Brassica campestris, and its value was lower than that of the commercial herbicide flumioxazin. Subsequently, a valid and reliable 3-dimensional quantitative structure-activity relationship (3D-QSAR) model was established to explore the relationship between the different substituted phenyl groups and herbicidal activity of the target compounds. Meanwhile, the deep-seated structure-activity relationship of compounds 6 u and 6w was further investigated by the density functional theory (DFT) theoretical calculation. Besides, the potential action mechanism of the target compound was preliminarily studied by molecular docking. From these findings, compound 6c deserves further exploration as a promising novel natural product-derived green agro-herbicidal lead compound.
A pair of previously undescribed enantiomers (1 and 2) featuring a terpenylated coumarin structure were isolated from the roots of Notopterygium incisum. Their structures were elucidated using spectroscopic evidence obtained from MS and NMR, complemented by ECD calculations. Compounds 1 and 2 demonstrated anti-inflammatory activity by inhibiting nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages at a concentration of 15 μM.
Previous study showed that the marine-derived Streptomyces sp. ZZ735 produced novel antiglioma compounds with rare structural backbones in rice solid medium. In this study, further investigation of the metabolites produced by the same Streptomyces actinomycete in MSC liquid medium resulted in the isolation and identification of seven glutarimide derivatives. The isolated compounds were identified as actiphenol (1), (E)-2,3-dehydroanhydrocycloheximide (2), anhydroisoheximide (3), 2,3-dehydro-α-epi-isocycloheximide (4), streptoglutarimide K (5), streptoglutarimide L (6), and cycloheximide acid B (7) based on HRESIMS data, extensive NMR spectral analyses, ECD calculations, NMR calculations, and comparison with reference data. Streptoglutarimide K (5), streptoglutarimide L (6), and cycloheximide acid B (7) were three previously undescribed compounds. Antiglioma activity evaluation by the sulforhodamine B assay indicated that all seven glutarimide derivatives had activity in inhibiting the proliferation of human glioma cells with IC50 values of 8.5–19.7 μM for U87MG cells and 12.4–24.3 μM for U251 cells, of which cycloheximide acid B was the most active compound with IC50 values of 8.5 μM for U87MG cells and 12.4 μM for U251 cells.
A green 1,3-dipolar multicomponent cycloaddition reaction using an ionic liquid under ultrasonic conditions afforded a sulfonyl-substituted spiro[indoline-3,2′-pyrrolidin]-2-one in high yield. FT-IR, 1D/2D NMR, NOESY, HRMS, and HPLC analyses were used to confirm its structure and stereochemistry and demonstrated a chromatographic purity of over 99%, permitting reliable SAR analysis. Preliminary SAR analysis indicated that para-electron-withdrawing arylsulfonyl substituents were associated with enhanced antiproliferative potency. The lead sulfonyl spirooxindole exhibited low-micromolar antiproliferative activity against MCF-7, A549, and HCT-116 cells and induced apoptosis accompanied by G0/G1 cell-cycle arrest. Molecular docking and dynamics simulations suggested a stable interaction with the p53-binding cleft of MDM2, supporting the potential of this scaffold as a p53-MDM2 modulator for further anticancer optimization.
Two new acylated iridoid glycosides, named scrophularidoids A (1) and B (2), together with ten known compounds, 6-O-α-L-(2′′-O-p-methoxycinnamoyl)rhamnopyranosylcatalpol (3), 6-O-[(2′′,4′′-di-O-acetyl-3′′-O-trans-cinnamoyl)-α-L-rhamnopyranosyl]-catalpol (4), scrophuloside A4 (5), scrophuloside B4 (6), scrophuloside B (7), 8-O-feruloylharpagide (8), 8-O-E-p-methoxycinnamoylharpagide (9), 8-O-(p-coumaroyl)harpagide (10), harpagoside (11), and harpagoside-B (12) were isolated from Scrophularia ningpoensis. The structures of these compounds were elucidated based on spectroscopic analysis and ECD calculation. Their insulin resistance-improving activity was evaluated using a glucose consumption assay in glucosamine-induced insulin-resistant HepG2 cells. Compounds 1, 2 and 10 displayed significant insulin resistance-improving activity with EC50 values of 7.87, 18.29, and 64.31 μM, respectively.
The phytochemistry of the Australian native plant Olearia viscidula (Asteraceae) has been investigated for the first time, with three new and two known furanoclerodanes, and four flavones isolated. The new natural products were identified as 18-O-succinyl kingidiol (0.81% w/w), 18-dehydrokingidiol, and 12-hydroxyhautriwaic acid. Kingidiol was also present in the crude extract, with large quantities of the diterpene readily isolated (1.24% w/w) from the crude extract following saponification. The known ent-clerodane jewenol A, and the flavones gardenin B, jaceosidin, 7-methylsudachitin and xanthomicrol were also isolated from the plant. This study demonstrates that O. viscidula is an abundant source of ent-clerodanes and flavones, and confirms that ent-clerodanes are common in Olearia in the Australasian lineage of Asteraceae, with similarities to the South American genus Baccharis.
An unusual linear nor-triterpene derivative named lacrymaric acid (1) was isolated from Lacrymaria lacrymabunda caps. This compound was revealed in TLC-bioautography as antibacterial against various Staphylococcus aureus strains, including methicillin-resistant clinical isolates (MRSA). The structure of 1 was unambiguously elucidated by spectroscopic analyses (HR-ESI-MS, 1D and 2D NMR) as an acyclic carboxylated nor-triterpene putatively derived from squalene.
Three previously undescribed sesquiterpenoids (1–3), together with three known compounds (4–6), were isolated from the whole plants of Euphorbia dentata. Their structures were elucidated on the basis of comprehensive spectroscopic analyses, including NMR and HRESIMS, as well as comparison of experimental and calculated ECD spectra. The cytotoxicity of compounds 1–6 against HepG2 cells was evaluated using the MTT assay, and none of them showed significant cytotoxic activity at 50 μM.
A new sesquiterpenoid, rugosic acid E (1), along with three known secondary metabolites (2-4) were isolated from the chloroform-soluble layer fraction of the leaves of Rosa rugosa using diverse chromatographic techniques. The planar structures were elucidated by NMR and HRESIMS spectroscopic methods. Furthermore, the absolute configuration of rugosic acid E (1) was determined by comparison of ECD calculations. All the compounds were evaluated for antibacterial activity against two Gram-positive bacteria, Bacillus subtilis and Bacillus cereus. Only compounds 1 and 2 exhibited weak antibacterial activity at a concentration of 400 μg per disk.
Bruguiera gymnorrhiza-associated fungi are valuable sources of bioactive natural products for drug discovery. Chemical investigation of a Bruguiera gymnorrhiza-associated fungus Aspergillus aculeatus GXMU-2 yielded to four indole-phenolic acid ester hybrid compounds (1−4). Compound 1 exhibited selective cytotoxicities among several human cancer cells. Molecular docking revealed compound 1 possessed potential Tdp1 inhibitory activity via multiple hydrogen bonds with catalytic residues, supporting its Tdp1 inhibition and Top1cc-trapping ability. This study enriches the structural diversity of indole-phenolic acid ester hybrid compounds and provides a promising lead compound for the development of Tdp1-targeted inhibitory agents.
A new tetranor-cycloartane-type triterpenoid glycoside, named phlomodinartan, was isolated from the aerial parts of Phlomoides ostrowskiana. Its structure was elucidated using 1D and 2D NMR spectroscopy and HR-ESI-MS analysis. The hypolipidemic activity of phlomodinartan was evaluated in rat models of experimental hyperlipidemia. The compound significantly reduced serum cholesterol and triglyceride levels in all models. In the vitamin Ds-cholesterol model, phlomodinartan reduced cholesterol by 46% and triglycerides by 32%, showing stronger activity than the reference herbal preparation polysponin. In the hydrocortisone-induced model, cholesterol and triglyceride levels decreased by 21% and 22%, respectively. The compound also showed antioxidant activity, decreasing malondialdehyde levels by 28% and increasing catalase and superoxide dismutase activities by 51% and 73%, respectively. Acute toxicity studies showed low toxicity with LD50 > 3000 mg/kg. These results indicate that phlomodinartan is a promising natural hypolipidemic and antioxidant agent.
Three new compounds, arnebinols F (1) and G (2) and 5-propionyloxy-1,4- naphthoquinone (3), were isolated from the petroleum ether soluble fraction of the ethanol extract of Arnebia euchroma I. M. Johnst. The structures of 1-3 were comprehensively analyzed using high-resolution electrospray ionization mass spectrometry and oneand two-dimensional nuclear magnetic resonance spectroscopy. The antitumor activity of compounds 1-3 was evaluated, and the results indicated that compound 2 exhibited preliminary activity against the HeLa and SiHa cell lines, with IC50 values of 3.9 and 15.7 & micro;M, respectively. The preliminary inhibitory activity of compound 2 likely originated from the presence of a terminal double bond and a vinyl group.
Pectin was extracted from semi-ripe fruits of Tamarindus indica and characterized for its physicochemical, structural, and antioxidant properties. The extracted pectin showed a slightly acidic pH (4.4), methoxy content of 6.32%, and degree of esterification of 52.8%, classifying it as high-methoxyl pectin. The anhydrouronic acid content was 67.93%, indicating a relatively high galacturonic acid composition. Monosaccharide analysis revealed the presence of glucose, fructose, galactose, and arabinose as major neutral sugars. The extract also contained phenolic and flavonoid compounds. Antioxidant activity assessed by DPPH, ABTS, hydroxyl radical scavenging, FRAP, and reducing power assays showed strong concentration-dependent activity with IC50 values of 58-62 & micro;g/ml. UV-Vis and FTIR analyses confirmed characteristic structural features of pectic polysaccharides. Overall, the results demonstrate that red tamarind-derived pectin possesses promising physicochemical and antioxidant properties, suggesting its potential as a natural functional polysaccharide for food and related applications.
Three new prenylated phloroglucinols, designated as hyperyicinols A-C (1-3), were isolated from Hypericum henryi. Their structures were unambiguously elucidated via comprehensive spectroscopic analyses, including HRESIMS, as well as 1D and 2D NMR spectroscopy. Furthermore, the anti-neuroinflammatory activities of compounds 1-3 were evaluated in LPS-induced BV-2 microglial cells, with IC50 values of 17.5 +/- 1.2, 8.7 +/- 0.4 and 6.3 +/- 0.8 mu M, respectively. Additionally, all three compounds dose-dependently suppressed the secretion of pro-inflammatory cytokines including TNF-alpha, IL-6, and IL-1 beta.
The anti-diabetic potential of Fagonia indica leaf, seed, and flower extracts was assessed through phytochemical, in vitro, in silico, and in vivo analyses. Phytochemical screening revealed high concentrations of phenols (522.74 f 0.05 & micro;g/mL in leaves), flavonoids, glycosides, and alkaloids. Further LC-MS analysis identified key bioactive compounds. These included chlorogenic acid (known for glucose-lowering properties), arbutin (implicated in glycemic control), isorhamnetin (noted for antioxidant and anti-diabetic activities), and ursolic acid (documented for its role in glucose metabolism). Ethanolic extracts showed the highest antioxidant potency. DPPH scavenging reached 91.21 f 1.39%, and hydroxyl radical scavenging was 94.70 f 2.19%. The alpha-amylase inhibition assay also showed strong anti-diabetic effects. Seed and flower extracts had the lowest IC50 (0.41 ng/ & micro;L), even lower than metformin (65.00 f 1.44%). Molecular docking revealed strong binding affinities for ursolic acid (-10.0 kcal/mol), which may regulate glucose metabolism, and for kaempferol (-8.6 kcal/mol), implying increased insulin sensitivity. ADMET studies indicated favorable pharmacokinetics and low toxicity risks, supporting translational potential. In vivo experiments further confirmed significant reductions in fasting blood glucose levels (386.33 f 14.81 mg/dL) compared to diabetic control (510.66 f 11.17 mg/dL). They also showed lower HbA1c levels (4.9 f 0.05% vs. 9.8 f 0.05%) and improved lipid profiles (normalized triglycerides, HDL, and LDL). The extracts exhibited nephroprotective effects (reduced creatinine and urea levels) and hepatoprotective effects (normalized ALT, AST, and ALP levels), surpassing metformin in both safety and efficacy.
Phytochemical investigation of the heartwood of Pterocarpus erinaceus Poir. afforded three new diphenylpropane derivatives, erinaceusins A-C (1-3). Their structures were elucidated by comprehensive spectroscopic analyses, including 1D and 2D NMR, HRESIMS, UV, and IR data, and their absolute configurations were assigned by comparing experimental electronic circular dichroism (ECD) spectra with time-dependent density functional theory (TDDFT)-calculated data. Compounds 1-3 showed moderate anti-inflammatory activity with IC50 values ranging from 43.2 to 56.7 & micro;M.
Three cardenolide glycosides (1-3), including two undescribed ones (1 and 2), were isolated from the bulbs of Ornithogalum ponticum. Analysis of their one- and two-dimensional NMR spectroscopic data allowed the structures to be identified as 5(3,11 alpha,14,19-tetrahydroxy-3(3-[(alpha-L-quinovopyranosyl)oxy]-card-20(22)-enolide (1), 3(3[(O-alpha-L-arabinopyranosyl-(1-*4)-alpha-L-rhamnopyranosyl)oxy]-11 alpha,14-dihydroxy-5(3-card-20(22)-enolide (2), and 5(3,11 alpha,14-trihydroxy-19-oxo-3(3-[(alpha-L-quinovopyranosyl)oxy]-card-20(22)-enolide (3). Compounds 1-3 exhibited more potent cytotoxicity than cisplatin against A549 human lung adenocarcinoma cells with IC50 values of 0.034, 0.051, and 0.052 & micro;M, and against SBC-3 human small-cell lung cancer cells with IC50 values of 0.044, 0.052, and 0.067 & micro;M, respectively.
Three previously undescribed cassane-type diterpenoids, caesmimo B5 (1) and caesmimo B6/B7 (2/3) were isolated and identified from the seeds of Hultholia mimosoides. Their structures were established based on extensive spectroscopic methods, including high-resolution mass spectrometry (HR-MS), ultraviolet spectrum (UV), infrared spectroscopy (IR), and one-dimensional/two-dimensional nuclear magnetic resonance (1D/2D NMR). Their absolute configurations were confirmed by comparing experimental electronic circular dichroism data with calculated values. Structurally, compound 1 is rare 16-degradative norcassane-type diterpenoid. All isolated compounds were evaluated for their cytotoxic effects against NRK-52E cells at a concentration of 50 & micro;M using MTT assay.
