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.

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.

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.

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.

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.

Two new steroidal alkaloids from the rhizomes of Veratrum nigrum L. and their anti-TYLCV activity.

Two new steroidal alkaloids (1-2), together with seven known related steroidal alkaloids (3-9), were isolated from the rhizomes of Veratrum nigrum L. Their structures were elucidated by extensive spectroscopic analysis, and by comparison with literature data. Compound 1 possessed a rare 1, 3-oxazolidine unit within varazine-type alkaloids, and 2 was a 9-hydroxy-4-one derivative of 3-veratroylgermine. All isolates were evaluated inhibit tomato yellow leaf curl virus (TYLCV) activity. Compounds 5 and 7 (40 µg/mL) showed a significant anti-TYLCV activity in the host Nicotiana benthamiana with inhibition rates 74.6% and 63.4%, respectively, which are higher than that of the positive control ningnanmycin (51.4%).

Hyperfols A and B: Two Highly Modified Polycyclic Polyprenylated Acylphloroglucinols from Hypericum perforatum.

Two novel polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperfols A (1) and B (2), and two known biosynthetically related precursors (3 and 4) were isolated from Hypericum perforatum. Compound 1 possesses an unprecedented 2,3-seco-PPAP with a fused 5/5/9/5 tetracyclic skeleton, and 2 features a 30-norPPAP. Their structures were established by spectroscopic analysis, computer-assisted structure elucidation software, and electronic circular dichroism calculations. Moreover, compounds 1 and 4 exhibit significant cytotoxicity against human erythroleukemia cells by inducing cell apoptosis.

Stemtuberolines A-G, new alkaloids from Stemona tuberosa and their anti-TMV activity.

Three new tuberostemoamide-type alkaloids, stemtuberolines A-C (1-3), four new stenine-type alkaloids, stemtuberolines D-G (4-7), together with five known Stemona alkaloids (8-12), were isolated from the roots of Stemona tuberosa. Their structures were elucidated on the basis of comprehensive spectroscopic data analysis. Stemtuberoline C (3) exhibited significant anti-TMV activity with an inhibition rate of 60.48% at the concentration of 50 µg/mL, while that of ningnamycin, the positive control, was 52.89%.

Seven new anthranilamide derivatives from Aconitum apetalum.

Seven new anthranilamide derivatives, acoapetalines A-G (1-7), including one new naturally occurring compound (7), together with six known ones (8-13) were isolated from the whole plants of Aconitum apetalum. Their structures were established on the basis of extensive spectroscopic analyses (IR, UV, HRESIMS, 1D and 2D NMR). All compounds were evaluated for their anti-tobacco mosaic virus (anti-TMV) activities. The results showed that compound 10 exhibited significant anti-TMV activity with an inhibition rate of 67.57% (100 µg/mL), which was higher than that of ningnamycin (52.89%).

Chromanopyrones and a flavone from Hypericum monogynum.

Six new compounds, including three pyrone derivatives (2-4), one new flavone (5), and two new naturally-occurring compounds (1 and 6), together with 16 known compounds were isolated from the leaves and twigs of Hypericum monogynum. In addition, compounds 2-4 are racemates. Their structures and absolute configurations were determined on the basis of extensive analysis of spectroscopic data and ECD calculation. All compounds were evaluated for the inhibitory effects on α-glucosidase, compounds 1, 5, and 7 showed moderate inhibitory activities with IC50 values of 161.46, 257.78, and 11.54µg/ml, respectively. Compound 8 exhibited weak anti-oxidant activity with IC50 value of 12.55µg/ml.