Cardiac glycosides from Streblus asper with potential antiviral activity.

Ten undescribed cardiac glycosides, strasperosides A-J, together with twelve known analogues, were isolated from Streblus asper Lour. Their structures were elucidated on the basis of spectroscopic analysis, electronic circular dichroism data, and chemical methods. These cardiac glycosides showed diversity in steroid skeleton and sugar moiety. Strasperosides A and B are a pair of unusual stereoisomers featuring different orientation of the lactone motif. Ten cardiac glycosides demonstrated potent antiviral effects on HSV-1 in vitro with the IC50 values from 0.19 ± 0.08 to 1.03 ± 0.25 µM and the therapeutic indices from 66.61 ± 5.08 to 326.75 ± 11.75.

Formyl phloroglucinol meroterpenoids from the leaves of Eucalyptus globulus subsp. maidenii and their ATP-citrate lyase inhibitory activities.

Three new formyl phloroglucinol meroterpenoids, eumaidials A-C (1-3), were isolated from the leaves of Eucalyptus globulus subsp. maidenii, along with ten known analogues (4-13). Their chemical structures were determined by various spectral data and electronic circular dichroism calculations. Eumaidial A (1) is the first ß-caryophyllene-based formyl phloroglucinol meroterpenoids from the genus Eucalyptus. Compounds 1-4 and 10 exhibited ATP-citrate lyase inhibitory activities, and compounds 2 and 3 suppressed the hepatocyte lipogenesis.

Two New Cytotoxic Maytansinoids Targeting Tubulin from Trewia nudiflora.

Two new maytansinoids, N-methyltreflorine (1: ) and methyltrewiasine (2: ), were isolated from the dried fruits of Trewia nudiflora, together with three known congeners (3:  - 5: ). Their structures were elucidated by spectroscopic methods, and the absolute configuration of 1: and 2: was determined by X-ray crystallographic analysis. Compounds 1:  - 5: exhibited strong cytotoxicity against human tumor cell lines, including HeLa, MV-4 - 11, and MCF-7, with IC50 values ranging from 0.12 to 11 nM. Compounds 1: and 4: also showed inhibitory activity against the MCF-7/ADR cell line with IC50 values of 13 and 28 nM, respectively. Compounds 1: and 2: significantly inhibited tubulin polymerization in vitro with IC50 values of 3.6 and 3.2 µM, respectively.

Two New Oleanane-Triterpenoid Saponins from Clinopodium gracile.

Two new oleanane-triterpenoid saponins, clinograsaponins A (1) and B (2), together with twelve known ones (3-14), were isolated from the whole herb of Clinopodium gracile (Bentham) Matsumura. Their structures were determined by spectroscopic analysis and chemical method. All the isolated compounds were evaluated for their activities against ATP-citrate lyase (ACLY) and nuclear factor kappa B (NF-κB).

Polyprenylated acylphloroglucinol meroterpenoids with PTP1B inhibition from Hypericum forrestii.

Three new polyprenylated acylphloroglucinol meroterpenoids, hyperiforins A-C (1-3), were isolated from Hypericum forrestii (Chittenden) N. Robson, together with twelve known analogues (4-15). Their structures were established by extensive physical and spectroscopic data analysis. Compounds 1, 2, 5, 7, and 13-15 showed potent inhibitory effects on protein tyrosine phosphatase 1B with IC50 values from 6.63 ± 2.40 to 14.21 ± 3.51 µM.

Hyperprins A and B, Two Complex Meroterpenoids from Hypericum przewalskii.

Hyperprins A (1) and B (2), two polyprenylated acylphloroglucinol related meroterpenoids with undescribed carbon skeletons, were isolated from Hypericum przewalskii. Compound 1 possesses a new 6/6/6/6/5/5 hexacyclic system with an unprecedented tetracyclo[10.3.1.03,8.08,12]hexadecane motif. Compound 2 features a unique 6/8/6/6 tetracyclic scaffold. Their structures were determined by spectroscopic data, chemical method, and X-ray crystallography. Compound 1 showed antiproliferation activity against the MV-4-11 cell line, and the p-bromobenzoate derivative of 2 displayed PTP1B inhibition.

Enantiomeric pairs of meroterpenoids from Rhododendron fastigiatum.

Five pairs of optically pure meroterpenoid enantiomers (1a/1b-5a/5b) and two known compounds (6 and 7) were isolated from Rhododendron fastigiatum. Compounds 1a/1b-5a/5b were resolved from naturally scalemic mixtures by chiral HPLC. Their structures were elucidated by spectroscopic methods, X-ray crystallographic experiments, and ECD analyses. Compounds 1a/1b, 2a/2b, 3b, 4a/4b, and 5a/5b were new meroterpenoids with different polycyclic systems. Two enantiomeric pairs (2a/2b and 3a/3b), 6, and 7 exhibited inhibitory effects on protein tyrosine phosphatase 1B (PTP1B) in vitro.

New triterpenoids and PTP1B inhibitory constituents of Pseudolarix amabilis.

Six new triterpenoids, pseudolarins A-F (1-6), were isolated from the twigs of Pseudolarix amabilis, together with four known triterpenoids (7-10) and five known diterpenoids (11-15). Their structures were determined by extensive spectroscopic analysis, and the absolute configuration of 1 was assigned by single-crystal X-ray diffraction. Compound 1 is a 3,4:9,10-diseco-cycloartane triterpenoid possessing an unprecedented 5/5/7/6/5/6/5 ring system. Compounds 1, 5, 7, 9-11, and 13 showed inhibition against protein tyrosine phosphatase 1B (PTP1B) in vitro.

[Studies on alkaloid constituents of Fritillaria yuminensis].

Twelve alkaloids were isolated from the bulbs of Fritillaria yuminensis by column chromatography over silica gel, ODS, and Sephadex LH-20, as well as RP-HPLC. Their structures were identified mainly by NMR and MS analyses as yubeinine(1), imperialine(2), delavinone(3), tortifoline(4), hupehenizioiside(5), imperialine-ß-D-glucoside(6), kuroyurinidine(7), pengbeisine A(8), walujewine A(9), peimisine-3-O-ß-D-glucopyranoside(10), solanidine-3-O-α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranoside(11), and solanidine-3-O-α-L-rhamnopyranosyl-(1→2)-[ß-D-glucopyranosyl-(1→4)]-ß-D-glucopyranoside(12). Compounds 4-12 were obtained from F. yuminensis for the first time.

[Flavonoids with PTP1B inhibition from Broussonetia papyrifera].

Eleven flavonoids were isolated from the twigs of Broussonetia papyrifera by column chromatography over silica gel,ODS,MCI gel,and Sephadex LH-20,as well as RP-HPLC.Their structures were identified by spectroscopic methods including NMR,MS,UV,and IR as broupapyrin A(1),5,7,3',4'-tetrahydroxy-3-methoxy-8-geranylflavone(2),8-prenylquercetin-3-methyl ether(3),broussonol D(4),broussoflavonol B(5),uralenol(6),broussonol E(7),8-(1,1-dimethylallyl)-5'-(3-methylbut-2-enyl)-3',4',5,7-tetrahydroxyflanvonol(8),broussoflavonol E(9),4,2',4'-trihydroxychalcone(10),and butein(11).Compound 1 is a new isoprenylated flavonol.Compounds 3,6,10,and 11 were obtained from the genus Broussonetia for the first time,and 4 and 7 were firstly discovered in B.papyrifera.Compounds 1-5 and 7-9 showed significant inhibitory effects on PTP1 B with IC50 values ranging from(0.83±0.30) to(4.66±0.83) µmol·L-1.

Isosteroidal alkaloids from the bulbs of Fritillaria tortifolia.

Three new isosteroidal alkaloids, frititorines A-C (1-3), were isolated from the bulbs of Fritillaria tortifolia, together with ten known ones (4-13). Their structures were elucidated by extensive spectroscopic analyses, chemical methods, and single-crystal X-ray crystallographic analysis. Compound 1 is the first 5ß-cevanine alkaloid with a cis A/B ring junction from the Fritillaria genus. Compound 2 is the first example of glycosylated isosteroidal alkaloid N-oxide. Compound 1 showed significant relaxant effect on Ach-induced tracheal contraction with pA2 and EC50 values equivalent to those of aminophylline.

Flavans and diphenylpropanes with PTP1B inhibition from Broussonetia kazinoki.

Three new (1a/1b and 2b) and five known flavans (2a, 6a/6b, 7, and 8), one new flavan glycoside (3), and two new (4 and 5) and six known 1,3-diphenylpropanes (9-14) were isolated from the twigs of Broussonetia kazinoki. Compounds 1, 2, and 6 are scalemic mixtures, and were resolved by chiral HPLC to provide 1a/1b, 2a/2b, and 6a/6b. The structures of these compounds were elucidated by extensive spectroscopic methods, including NMR, MS, and ECD analyses. Compounds 1, 2, 5, 8, 9, 11, and 12 showed in vitro inhibition of protein tyrosine phosphatase 1B (PTP1B).

5,4'-Dihydroxy-7,8-dimethoxyflavanone and Aliarin from Dodonaea viscosa Are Activators of PPARγ.

PPARγ agonists are widely used medications in diabetes mellitus therapy. Their role in improving adipose tissue function contributes to antidiabetic effects. The extracts of Dodonaea viscosa have been reported to exert antidiabetic activity. However, the effective mediators and the underlying mechanisms were largely unknown. In this study, we investigated the action on PPARγ transactivation and adipocyte modulation of two typical flavonoid constituents from D. viscosa, 5,4'-dihydroxy-7,8-dimethoxyflavanone and aliarin. Our results showed that 5,4'-dihydroxy-7,8-dimethoxyflavanone and aliarin were potential partial PPARγ agonists. The compounds induced adipogenesis in 3T3-L1 cells, with an upregulated adiponectin mRNA level and enhanced insulin sensitivity. The favorable effects of 5,4'-dihydroxy-7,8-dimethoxyflavanone, aliarin, and other flavonoid constituents on adipocytes might contribute to the antidiabetic efficacy of D. viscosa.

Isoprenylated phenolic compounds with PTP1B inhibition from Morus alba.

Two new Diels-Alder adducts, albasins A and B (1 and 2), one new isoprenylated 2-arylbenzofuran, albasin C (3), one new isoprenylated flavone, albasin D (4), together with sixteen known phenolic compounds, were isolated from the root bark of Morus alba. Their structures were elucidated by extensive spectroscopic analysis, including NMR, MS, and ECD data. All the new compounds and most of the known ones showed significant inhibitory effects on PTP1B in vitro with IC50 values ranging from 0.57 to 7.49µM.

New Isoprenylated Phenolic Compounds from Morus laevigata.

Two new isoprenylated flavonoids, laevigasins A and B (1 and 2, resp.), and one new isoprenylated 2-arylbenzofuran, leavigasin C (3), together with eight known compounds, 4-11, were isolated from the twigs of Morus laevigata. Their structures were elucidated by spectroscopic methods. Laevigasin A (1) showed significant inhibitory effect on α-glucosidase in vitro. Notabilisin E (5), taxifolin (10), and hultenin (11) inhibited PTP1B phosphatase activity in vitro.

Inhibitory Effects of (2'R)-2',3'-dihydro-2'-(1-hydroxy-1-methylethyl)-2,6'-bibenzofuran-6,4'-diol on Mushroom Tyrosinase and Melanogenesis in B16-F10 Melanoma Cells.

(2'R)-2',3'-Dihydro-2'-(1-hydroxy-1-methylethyl)-2,6'-bibenzofuran-6,4'-diol (DHMB) is a natural compound extracted from Morus notabilis. It was found that DHMB acts as a competitive inhibitor against mushroom tyrosinase with a Ki value of 14.77 µM. Docking results further indicated that it could form strong interactions with one copper ion with a distance of 2.7 Å, suggesting the mechanism of inhibition might be due to chelating copper ions in the active site. Furthermore, melanin production in B16-F10 murine melanoma cells was significantly inhibited by DHMB in a concentration-dependent manner without cytotoxicity. The results of western blotting also showed that DHMB decreased 3-isobuty-1-methxlzanthine-induced mature tyrosinase expression. Taken together, these findings indicated that DHMB may be a new promising pigmentation-altering agent for agriculture, cosmetic, and therapeutic applications.

Isoprenylated Flavonoids with PTP1B Inhibition from Ficus tikoua.

Two new isoprenylated flavanones, ficustikousins A and B (1 and 2), together with seven known compounds (3-9) were isolated from the whole plant of Ficus tikoua (Moraceae). The structures of the new compounds were elucidated on the basis of spectroscopic methods. Compounds 1-7 exhibited moderate inhibitory activities against PTP1B in vitro.

Triterpenoids and α-glucosidase inhibitory constituents from Salacia hainanensis.

Thirteen triterpenoids (1-13), including two new lupane triterpenoids, salacinins A and B (1 and 2), as well as one new friedelane triterpenoid, salacinin C (3), were isolated from the roots and stems of Salacia hainanensis. The structures of new compounds were elucidated by extensive spectroscopic analysis including 1D and 2D NMR, and MS experiments. Compound 1 possesses rare 2,3-seco-lupane skeleton. Compounds 4, 6 and 7 showed inhibitory effects on α-glucosidase in vitro.

[Phenolic compounds from Rhododendron phaeochrysum var. agglutinatum].

Eight phenolic compounds were isolated from Rhododendron phaeochrysum var. agglutinatum and their sructures were identified as phaeochrysin (1), (2R)-4-(3',4'-dihydroxyphenyl) -2-butanol (2), (-) -rhododendrol (3), rhododendrin (4), (+) -isolariciresinol (5), (-) -lyoniresinol (6), lyoniresinol-9'-O-ß-D-xylopyranoside (7), and dihydrodehydrodiconiferyl-3a-O-α-L-rhamnopyranoside (8). Compound 1 is new, and compounds 2, 5-8 were isolated from this plant for the first time.

2-Arylbenzofuran and tyrosinase inhibitory constituents of Morus notabilis.

Phytochemical investigation of the stem of Morus notabilis led to the isolation and characterization of 10 compounds of 2-arylbenzofurans (1-10), including two new compounds, (2'R)-2',3'-dihydro-2'-(1-hydroxy-1-methylethyl)-2,6'-bibenzofuran-6,4'-diol (1) and 5,6-dimethoxy-2-(3-hydroxy-5-methoxyphenyl)benzofuran (2). Moracins O (6) and P (10) showed inhibitory effects on mushroom tyrosinase with IC50 values being lower than that of kojic acid.