Quassinoids from Twigs of Harrisonia perforata (Blanco) Merr and Their Anti-Parkinson's Disease Effect.

Six new C-20 and one new C-19 quassinoids, named perforalactones F-L (1-7), were isolated from twigs of Harrisonia perforata. Spectroscopic and X-ray crystallographic experiments were conducted to identify their structures. Through oxidative degradation of perforalactone B to perforaqussin A, the biogenetic process from C-25 quassinoid to C-20 via Baeyer-Villiger oxidation was proposed. Furthermore, the study evaluated the anti-Parkinson's disease potential of these C-20 quassinoids for the first time on 6-OHDA-induced PC12 cells and a Drosophila Parkinson's disease model of PINK1B9. Perforalactones G and I (2 and 4) showed a 10-15% increase in cell viability of the model cells at 50 µM, while compounds 2 and 4 (100 µM) significantly improved the climbing ability of PINK1B9 flies and increased the dopamine level in the brains and ATP content in the thoraces of the flies.

UPLC-Q-Orbitrap-MS/MS-Guided Isolation of Bioactive Withanolides from the Fruits of Physalis angulata.

Physalis angulata Linn. is an exotic Amazonian fruit that is commonly recognized as wild tomato, winter cherry, and gooseberry. While its fruit is known to contain many nutrients, such as minerals, fibers, and vitamins, few papers have investigated withanolide derivatives from its fruits. UPLC-Q-Orbitrap-MS/MS, which produces fragmentation spectra, was applied for the first time to guide the isolation of bioactive withanolide derivatives from P. angulata fruits. As a result, twenty-six withanolide derivatives, including two novel 1,10-secowithanolides (1 and 2) and a new derivative (3), were obtained. Compounds 1 and 2 are rare rearranged 1,10-secowithanolides with a tetracyclic 7/6/6/5 ring system. All structures were assigned through various spectroscopic data and quantum chemical calculations. Nine withanolide derivatives exhibited significant inhibitory effects on three tumor cell lines with IC50 values of 0.51-13.79 µM. Moreover, three new compounds (1-3) exhibited potential nitric oxide inhibitory effects in lipopolysaccharide-stimulated RAW264.7 cells (IC50: 7.51-61.8 µM). This investigation indicated that fruits of P. angulata could be applied to treat and prevent cancer and inflammatory-related diseases due to their potent active withanolide derivatives.

Active constituents with α-glucosidase inhibitory activities from Sabia parviflora.

To identify the active constituents with α-glucosidase inhibitory activities in Sabia parviflora, three new compounds, namely, sabiaparviflora A-C (1, 2 and 8), and seven known compounds were isolated from the plant by repeated column chromatography. The structures of the new compounds were identified by extensive application of spectroscopic methods, including 1H NMR, 13C NMR, IR and HR-ESI-MS. All compounds, except for compounds 3-5, 9 and 10 were isolated for the first time from S. parviflora. Their α-glucosidase inhibitory activities were evaluated for the first time by the PNPG method. Three compounds (1, 7 and 10) exhibited marked activities, with IC50 values ranging from 104 to 324 µM, and their structure-activity relationship is preliminarily discussed herein.

Munronin V with 7/7/6 tricarbocyclic framework from Munronia henryi harms inhibits tau pathology by activating autophagy.

Munronin V (1), isolated from Munronia henryi Harms, is the first example, to the best of our knowledge, of an unprecedented 7/7/6 tricarbocyclic framework featuring an unusual A,B-seco-limonoid ring. The structures of munronin V were established from extensive spectroscopic and electronic circular dichroism (ECD) analyses. The novel A,B-seco with two seven-membered lactones was formed as a result of Baeyer-Villiger oxidation. Compound 1 activated autophagy and inhibited Tau pathology as revealed by flow cytometric analyses, confocal imaging analysis and western blotting, and this effect was mediated by transcription factor EB (TFEB). These findings suggested that 1 might have potential as a compound for combating Alzheimer's disease.

Hyperpatone A, a polycyclic polyprenylated acylphloroglucinol with a rare 8/6/5/6/5 pentacyclic skeleton from Hypericum patulum.

Hyperpatone A (1), a highly oxidated polycyclic polyprenylated acylphloroglucinol (PPAP), along with a biosynthesized related PPAP (2) was isolated from Hypericum patulum under the guidance of LC-MS investigation. Architecturally, compound 1 represents the first PPAP with an unprecedented 8/6/5/6/5 pentacyclic skeleton and an intramolecular peroxy bridge, which might be derived from the [3.3.1]-type bicyclic polyprenylated acylphloroglucinol via the critical Baeyer-Villiger oxidation, decarboxylation, and intramolecular cyclization. The structures were established by extensive spectroscopic analysis, ACD software calculation, and quantum chemical computations. A plausible biogenetic pathway of 1 and 2 was also proposed. Importantly, both compounds exhibited moderate cytotoxic activities against the HEL cell line with the IC50 values ranging from 10.2 to 19.2 µM. Moreover, compound 1 showed an inhibitory effect on NO production in lipopolysaccharide-stimulated RAW264.7 cells at a lower concentration of 5 or 1 µM.

Maillard Reaction Products with Anti-Tobacco Mosaic Virus Activities Generated in Processed Thermopsis lanceolata R. Br. Seed Extract.

Six novel Maillard reaction products (MRPs) (1-6) were isolated from the processed Thermopsis lanceolata R. Br. seed extract, along with one biogenetically related intermediate (7). Compounds 1-4 possessed three rare dimerization patterns constructed by cytisine, whereas compounds 5 and 6 represented the first example of the addition products of cytisine and 5,6-dihydroxy-4-hexanolide. Their structures were elucidated by comprehensive spectroscopic data analysis and quantum chemistry calculations including GIAO 13C{1H} NMR and ECD calculation, combined with single-crystal X-ray diffraction analysis. Biologically, compound 3 displayed significant anti-tobacco mosaic virus activity compared with the positive control ningnanmycin.

Hypersampones A-C, Three Nor-Polycyclic Polyprenylated Acylphloroglucinols with Lipid-Lowering Activity from Hypericum sampsonii.

Hypersampones A-C (1-3), three unprecedented nor-polycyclic polyprenylated acylphloroglucinols (PPAPs), were isolated from Hypericum sampsonii. These compounds represent the first nor-PPAPs with an unexpected tetracyclic 6/5/5/6 ring system. Their structures were assigned through the analysis of detailed spectroscopic data, X-ray crystallography, and electronic circular dichroism calculations. Compound 1 significantly inhibited the accumulation of lipid in an oleic acid-treated HepG2 cell model by suppressing the protein expression of FAS and ACACA at 5 µM.

Novel flavonolignans from the roots of Indigofera stachyodes.

Two pairs of new enantiomeric flavonolignans, ±stachyols A and B (±1 and ± 2), along with two novel isoflavanelignans, stachyols C and D (3 and 4) were isolated from the roots of Indigofera stachyodes. Their chemical structures and absolute configurations were determined using nuclear magnetic resonance and comparison of experimental and theoretical electronic circular dichroism (ECD) spectra, as well as quantum chemical calculations. Of those compounds, 1 and 2 represented the first examples of flavonolignans with 5-deoxyflavonoids adduct phenylpropanoids. Moreover, 3 and 4 possess an unprecedented skeleton with isoflavanes adduct phenylpropanoids. The antioxidant activity was evaluated for all compounds in terms of ABTS+ and DPPH bioassays. Compounds 3 and 4 exhibited significant radical-scavenging activity in the ABTS+ assay, with IC50 values of 15.15 and 5.83 µM, respectively.

Three New Aglain Derivatives from Aglaia odorata Lour. and Their Cytotoxic Activities.

Three new aglain derivatives (1-3), one known aglain derivative (4), two known rocaglamide derivatives (5 and 6), four known triterpenoids (7-10), and three steroids (11-13) were isolated from Aglaia odorata Lour. Their structures were established through the analysis of detailed spectroscopic data and electronic circular dichroism calculations. Five compounds (1 and 4-7) exhibited cytotoxic activities on human leukemia cells (HEL) and human breast cancer cells with IC50 values in the range of 0.03-8.40 µM. In particular, the cytotoxicity of compound 5 was six times stronger than that of the positive control (adriamycin) in HEL cell lines.

Oreocharioside A-G, new acylated C-glycosylflavones from Oreocharis auricula (Gesneriaceae).

Seven new acylated C-glycosylflavones, oreocharioside A-G, together with two known compounds were isolated from the whole plant of Oreocharis auricula. Their structures were characterized by the comprehensive analysis of their NMR, IR, UV, CD spectra and HRESIMS data. All the new compounds were evaluated for the antioxidant and anti-inflammatory activities. The results showed that compounds 1 and 2 had significant DPPH and ABTS radical scavenging activities, with the IC50 values of 0.32-3.20 µg/mL. Compounds 2 and 3 exhibited the higher potency among all the new compounds in reducing TNF-α production.

Thermlanseedlines A-G, seven thermopsine-based alkaloids with antiviral and insecticidal activities from the seeds of Thermopsis lanceolata R. Br.

Seven undescribed thermopsine-based alkaloids (1-7), including one undescribed biogenetically related intermediate (7), were isolated from the seeds of Thermopsis lanceolata R. Br. Compound 1 possessed a 6/6-6 tricyclic skeleton, while compounds 2-6 represented three rare dimerization patterns constructed by quinolizidine alkaloids. Their structures were elucidated by comprehensive spectroscopic data analysis as well as ECD calculations. Biologically, compound 6 displayed significant anti-Tomato spotted wilt virus (TSWV) activity compared with the positive control ningnanmycin. Moreover, compound 1 exhibited good insecticidal activity against Aphis fabae with LC50 value of 25.2 mg/L.

Chemical constituents from the flowers of Hypericum monogynum L. with COX-2 inhibitory activity.

Hypericum monogynum L. (Hypericaceae) has been used as a folk Chinese medicine for the treatment of inflammatory related diseases. Cyclooxygenase-2 (COX-2) is a crucial target for the development of agents to treat inflammation. To search for anti-inflammatory compounds from traditional Chinese medicines, a chemical constituent study along with COX-2 inhibitory activity analysis was performed for this plant. In this study, sixteen chemical monomers, including three undescribed oxidative degradation polycyclic polyprenylated acylphloroglucinols (PPAPs, hypemoins C-E), two undescribed PPAPs (hypemoins A and B), and 11 known compounds, were identified from the flowers of H. monogynum. Their structures were characterized by HRESIMS, NMR techniques, ECD, and single crystal X-ray diffraction. Four flavonoid derivatives showed remarkable COX-2 inhibitory activities, with IC50 values ranging from 0.220 ± 0.006 to 1.655 ± 0.098 µM. Among these compounds, the possible recognition mechanism between quercetin 3-(6″-O-caffeoyl)-ß-3-D-galactoside and COX-2 was predicted by molecular docking analysis. Moreover, the multidrug resistance reversal activities for the selected compounds were evaluated.

A new antimicrobial nor-friedelane-type triterpenoid and other constituents from Plectranthus glandulosus Hook. f. (Lamiaceae).

Chemical investigation of the ethanol extract from the whole plant of Plectranthus glandulosus led to the isolation of a new nor-triterpenoid (1) along with seventeen known compounds (2-18) including seven triterpenoids, nine flavonoids and one steroid. Their structures were established on the basis of 1D- and 2D-NMR, IR, and MS experiments, and by comparison of their spectroscopic data with those of similar compounds reported in the literature. The EtOH extract and some isolated triterpenoids (1-4 and 13) were subjected to in vitro antimicrobial assays against a panel of pathogenic microorganisms, including Gram-positive and Gram-negative bacteria, and fungi using broth microdilution method. The EtOH extract displayed moderate activity (MIC = 512 µg/mL) against Staphylococcus aureus MSSA1, Shigella flexneri SDINT and Cryptococcus neoformans H99. Compounds 1, 4 and 13 showed the most potent antimicrobial effect with MICs of 32-256 µg/mL.

Hepatoprotective Constituents of Total Dibenzocyclooctadiene Lignans from Schisandra chinensis Based on the Spectrum-Effect Relationship.

To scientifically clarify the hepatoprotective constituents of Fructus Schizandrae chinensis, eleven batches samples of total dibenzocyclooctadiene lignans (TDL) from Schisandra chinensis were prepared by using the optimum extraction technique. Characteristic high-performance liquid chromatography (HPLC) chromatograms were obtained through HPLC analysis technology, and the hepatoprotective effects of the eleven batches of TDL were evaluated by MTT assay. Based on the chemical and biological activity results, the spectrum-effect relationship between the characteristic HPLC fingerprints and the hepatoprotective effect of TDL was established using Minitab 16.0 data analysis software. On the basis of the spectrum-effect relationship, thirteen compounds (1-13) were obtained from the TDL by chemical natural product chemical separation and purification technology, and their structures were identified on the basis of the spectral data and the literature. Based on these compounds, thirteen common peaks among the thirty-three chromatographic peaks in the above HPLC fingerprints were identified. Our findings showed that some components, including, schisandrin B (2), schisandrin A (3), and schisandrol B (7) had significant roles in promoting hepatoprotective activity. Preliminary verification of the spectrum-effect relationship of TDL from S. chinensis was carried out, and the results confirmed that the activity of a composite of these three key components in optimal ratios was better than that of any individual compound, which potentially confirmed the reliability of the spectrum-effect relationship and the synergistic effects of traditional Chinese medicine.

Ten new nortriterpenes from Euphorbia resinifera and their anti-tomato yellow leaf curl virus activities.

Ten new nortriterpenes, euphorbiumrins A-J (1-10), together with three known analogues (11-13) were isolated from the latex of Euphorbia resinifera. Their structures were established on the basis of extensive spectroscopic analyses (IR, UV, HRESIMS, 1D and 2D NMR). Their inhibitions on tomato yellow leaf curl virus (TYLCV) were evaluated and compound 5 exhibited significant anti-TYLCV activity with an inhibition rate of 71.7% at concentration of 40 µg/mL.

Hypermoins A-D: Rearranged Nor-Polyprenylated Acylphloroglucinols from the Flowers of Hypericum monogynum.

Hypermonins A-D (1-4), four rearranged nor-polycyclic polyprenylated acylphloroglucinols (PPAPs) with unprecedented skeletons, together with two new biosynthesis related PPAPs (5 and 6) were isolated and identified from the flowers of Hypericum monogynum. Hypermoins A-D represented the first examples of highly modified norPPAPs characterized by a rare 7/6/6/5-tetracyclic system. From the biogenic synthesis pathway analysis, all isolates shared the same biosynthetic intermediate, and the addition of two methyls or one methyl to this intermediate through methyltranferase could generate different types of PPAPs (1-7). Their planner structures as well as absolute configuration were confirmed via spectroscopic analysis, ECD calculation, and X-ray crystallography. All isolates potentially reversed multidrug resistance (MDR) activity in both two cancer cells, HepG2/ADR and MCF-7/ADR. Specifically, hypermoin E (5) and hyperielliptone HA (7) were found to be the best MDR modulators with the reversal fold ranging from 41 to 236, which is higher than the positive control verapamil.

Hymoins A-D: Two Pairs of Polyprenylated Acylphloroglucinols from Hypericum monogynum and Their Light-Induced Transformation.

Hymoins A-D (1-4), two pairs of light-induced transformative polyprenylated acylphloroglucinols with an unprecedented pentacyclic skeleton, were isolated from the flowers of Hypericum monogynum. The first decarbonylative ring contraction of complex natural products was investigated by light irradiation. Their structures were elucidated by nuclear magnetic resonance analysis, X-ray crystallography, and electronic circular dichroism calculations. In addition, compound 3 showed moderate inhibition efficacy of the platelet-activating-factor-induced aggregation of rabbit platelets.

Discovery and synthesis of rocaglaol derivatives inducing apoptosis in HCT116 cells via suppression of MAPK signaling pathway.

Six rocaglaol derivatives were isolated from Dysoxylum gotadhora, and those compounds showed good cytotoxic activity with IC50 values ranging from 10 to 350 ng/mL against five different cancer cells. Obviously, further total synthesis of rocaglaol derivatives for medical chemistry study is of great significance. Then, twenty six rocaglaol derivatives including 25 new compounds were designed, synthesized, and evaluated for their cytotoxic activities against three human cancer cell lines: human colon cancer cells (HCT116), colorectal cancer stem cells (P6C), and human red leukocyte leukemia cells (HEL), using MTT assay. Most of derivatives showed good cytotoxic activities, with the lowest IC50 being 3.2 nM for HEL cells, which was 169 times stronger than that of the positive control (doxorubicin). Further mechanism study indicated that 11k could significantly suppress MAPK pathway in HCT116 cells, which may responsible for induction of apoptosis and cell cycle arrest.

Polycyclic polyprenylated acylphloroglucinol derivatives with neuroprotective effects from Hypericum monogynum.

A new polycyclic polyprenylated acylphloroglucinol (PPAP), hypermonin C (1), along with nine known PPAPs (2-10) were obtained from the leaves and twigs of Hypericum monogynum. The structures of the isolates were determined on the basis of extensive spectroscopic analysis. The neuroprotective effects of the isolates against several chemical-induced injuries in SH-SY5Y and PC12 cells were assessed, and most of the compounds exhibited significant protective effects at 10 µg/ml. Especially, three compounds (1, 3, and 7) showed excellent neuroprotective activity with a cell viability of 92.4% ∼ 95.8% in KCl-induced SH-SY5Y cell injury. Their preliminary structure-activity relationship was also discussed and the configuration of substituent in furohyperforin may be critical for the neuroprotective activity of PPAP derivatives.

Two new seco-polycyclic polyprenylated acylphloroglucinol from Hypericum sampsonii.

Hypsampsone A (1) and hyperhexanone F (2), two novel seco-polycyclic polyprenylated acylphloroglucinols, were isolated from Hypericum sampsonii. Hypsampsone A (1) features the first spirocyclic system fused with 5/6/5/5 tetracyclic skeleton. Hyperhexanone F (2) represents the second novel 1,2-seco-bicyclo[3.3.1]-PPAP skeleton. Their structures were established by extensive spectroscopic analysis, computer-assisted structure elucidation software, and calculated electronic circular dichroism spectra. A plausible biogenetic pathway of 1 was also proposed. Compounds 1 and 2 showed moderate multidrug resistance reversal activity to adriamycin (ADR) resistant cancer cell lines, HepG2/ADR and MCF-7/ADR, with the fold-reversals ranging from 16 to 38 at noncytotoxic concentration of 10 µM.