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.

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.

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.

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.

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.

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.

Cytotoxic phenolic constituents from Hypericum japonicum.

Nine undescribed compounds, including five xanthone derivatives, two flavonoids, one 2-pyrone derivative, and one undescribed naturally occurring compound, along with 30 known phenolic compounds, were isolated from Hypericum japonicum. In addition, hyperjaponols A and B were identified as racemates. The structures and absolute configurations of the undescribed compounds were determined by comprehensive MS, NMR spectroscopy, and electronic circular dichroism (ECD) calculations. The cytotoxic effects of the isolated compounds on two human tumour cell lines (HEL and MDA-MB-231) were evaluated by the MTT assay. Eighteen compounds showed good inhibitory activities against the HEL cell line, with IC50 values of 3.53-18.7 µM, while nine compounds exhibited moderate cytotoxicity against the MDA-MB-231 cancer cell line, with IC50 values ranging from 4.92 to 10.75 µM. Their preliminary structure-activity relationship of the isolated compounds was also discussed.

Hypermonins A and B, two 6-norpolyprenylated acylphloroglucinols with unprecedented skeletons from Hypericum monogynum.

Two new 6-norpolycyclic polyprenylated acylphloroglucinols (PPAPs), hypermonins A (1) and B (2), featuring an undescribed decahydroindeno[1,7-bc]furan ring system, were isolated from the leaves and twigs of Hypericum monogynum. These compounds are a pair of epimers with opposite configurations at the C-5 position. Their structures, including their absolute configurations, were determined by extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. A plausible biosynthetic pathway of 1 and 2 was also proposed. Compound 1 exhibited a significant protective effect against corticosterone-induced injury in PC12 cells.

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.

Diterpene alkaloids and diterpenes from Spiraea japonica and their anti-tobacco mosaic virus activity.

Five new naturally occurring natural products, including two atisine-type diterpene alkaloids (1 and 2), two atisane-type diterpenes (3 and 4), and a new natural product spiramine C2 (5), along with nine known ones (6-14), were isolated from the ethanolic extracts of the whole plant of Spiraea japonica var. acuminata Franch. Their structures were elucidated by extensive spectroscopic analysis. The anti-tobacco mosaic virus (TMV) activities of all the compounds were evaluated by the conventional half-leaf method. Six compounds (2, 3, 6, 7, 11, and 12) exhibited moderate activities at 100 µg/mL with inhibition rates in the range of 69.4-92.9%, which were higher than that of the positive control, ningnanmycin. Their preliminary structure-activity relationships were also discussed.

A novel isocoumarin with anti-influenza virus activity from Strobilanthes cusia.

Strobilanthes A (1), a novel isocoumarin with an unusual tetrahydro-4H-pyran-4-one moiety fused isocoumarin core skeleton, together with a known compound (2) was isolated from Strobilanthes cusia. Its chemical structures were elucidated by 2D NMR spectroscopy, mass spectrometry and single-crystal X-ray diffraction analysis. The biosynthetic pathway of 1 could be supposed to be originally derived from 3-methylisocoumarin, a product of AA-MA pathway. Both of two compounds displayed anti-influenza virus activity in vitro.

[Study on chemical constituents of Inula cappa].

Column chromatographies over silica gel, Sephadex LH-20, reverse phase C18, and MCI, and semi-preparative HPLC were used for separation and purification of constituents from Inula cappa. The 22 compounds were obtained and their strutures were determined by NMR and MS spectra data as nine flavonoids: luteolin (1), apigenin (2), chrysoeriol (3), artemetin (4), 2', 5-di- hydroxy-3, 6, 7, 4', 5'-pentamethoxyflavone (5), chrysosplenol C (6), apigenin-5-0-ß-D-glucopyranoside (7), luteolin-3-methyl, luteolin-3-methylether-4'-0-ß-D-glucopyranoside (8), luteolin-4'-0-ß-D-glucopyranoside (9); four triterpenes: darma-20, 24-dien- 3ß-0-acetate (10), darma-20, 24-dien-3ß-ol (11), epirfiedelanol (12), friedelin (13); three coumarins: scopoletin (14) , isosco- poletin (15) , scopolin(16) , and other types of compounds stigmasta-5, 22-dien-3ß-0-7-one (17), stigmasterol (18), palmitic acid (19), linoleic acid (20), linoleic acid methyl ester (21), (E) -9, 12, 13-trihydroxyoetadee-10-enoie acid (22). Compound 5 is a new natural product. Compounds 3-9, 15, 17, 21, and 22 were isolated from this genus for the first time.

Studies on cytotoxic pregnane sapogenins from Cynanchum wilfordii.

To investigate their cytotoxicity, seventeen C21-steroidal pregnane sapogenins 1-17 were isolated from the hydrolytic extracts of the roots of Cynanchum wilfordii. Among them, sapogenins 1-7 are new compounds, whose structures were determined by extensive analysis of spectroscopic data and X-ray crystallographic analysis. Especially, sapogenins with salicyl or vanilloyl group, and a new aberrant pregnane skeleton with ether linkage between C-12 and C-20 were found for the first time. Compound 1 revealed significant cytotoxicities on HL-60 (IC50 6.72µM) and MCF-7 (IC50 2.89µM), and compounds 14 and 15 also revealed strong inhibitory activities against K-562 (IC50 6.72µM) or MCF-7 (IC50 2.49µM), respectively.

Seco-pregnane steroidal glycosides from the roots of Cynanchum atratum and their anti-TMV activity.

Fifteen new seco-pregnane steroidal glycosides cynanosides A-O (1-15) together with twenty-seven known ones were isolated from the roots of Cynanchum atratum. The structures of 1-15 were determined by extensive analysis of spectroscopic data. The anti-tobacco mosaic virus (TMV) activity of these steroidal glycosides was screened by the conventional half-leaf method, enzyme-linked immunosorbent assay, and Western blot methods, most of them showed potent anti-TMV activity. Among them, compounds 1, 7, 13, 28 and 31 showed significantly anti-TMV activity with an IC50 value of 20.5, 18.6, 22.0, 19.2 and 22.2 µg/mL, respectively, and were much more effective than the positive control, ningnanmycin (IC50=49.6 µg/mL).

Alkaloids from Daphniphyllum oldhami.

Four new Daphniphyllum alkaloids, daphnioldhanines H-K ( 1- 4), along with 34 known alkaloids, were isolated from Daphniphyllum oldhami. The known alkaloid dehydrodaphnigraciline ( 5) is now reported as a natural product. Their structures were elucidated by spectroscopic methods, especially 2D NMR techniques. The effects against platelet aggregation of compounds 1, 3, and 5 were evaluated, and 3 showed stronger activity against platelet aggregation induced by PAF. This is the first report of quinolizidine alkaloids from the genus Daphniphyllum.