Labdane-type diterpenoids with cytotoxic and anti-inflammatory activities from the aerial parts of Hypoestes purpurea (L.) R. Br.

Two new ent-labdane diterpenoids, hypoestesins A-B (1-2) and five new labdane diterpenoids, hypopurolides H-L (3-7), were isolated from the aerial parts of Hypoestes purpurea. All of the structures were fully determined based on extensive analysis of 1H, 13C, 2D NMR, and HRESIMS data. The absolute configurations of 1-3 was established through comparing the experimental and calculated ECD curves and the structure of 5 was confirmed by single crystal X-ray diffraction experiment. Compounds 5-7 were unusual C23 labdane diterpenoids having a γ-acetonyl-α, ß-unsaturated γ-lactone unit and each assigned as C-15 epimeric mixture. Furthermore, cytotoxic and anti-inflammatory activities of 3-7 were evaluated. The results showed that 3 had remarkable cytotoxic activity against HL-60, A549, SMMC-7721, MDA-MB-231, and SW480 cancer cell lines with IC50 values ranging from 2.35 to 17.06 µM. Compound 4 showed moderate cytotoxic activity against HL-60 and SMMC-7721 cancer cell lines with IC50 values of 15.12 ± 0.53 and 12.92 ± 0.60 µM, respectively. Furthermore, compound 4 was also found to exhibit inhibitory activity against NO production in RAW 264.7 macrophages with IC50 values of 23.56 ± 0.99 µM, compared to the positive control L-NMMA with an IC50 value of 41.11 ± 1.34 µM.

Structurally diverse diterpenoids from the seeds of Caesalpinia minax Hance and their bioactivities.

Eight previously undescribed diterpenoids, caesamins A-H (1-8), were separated and identified from the seeds of Caesalpinia minax Hance. Their structures were characterized by extensive spectroscopic data and X-ray crystallographic analysis. Structurally, caesamin A (1) is the first cassane-type diterpenoid with a C23 carbon skeleton containing an unusual isopropyl. Caesamin F (6) represents the first example of cleistanthane diterpenoid from the genus Caesalpinia. Caesamins B (2) and F (6) exhibited inhibitory activity against LPS-induced nitric oxide production in RAW 264.7 macrophages with IC50 values of 45.67 ± 0.92 and 42.99 ± 0.24 µM, comparable to positive control 43.69 ± 2.62 µM of NG-Monomethyl-L-arginine. Furthermore, the chemotaxonomic significance of the isolates was discussed.

Spirocyclohexadienone-Type Neolignans with Neuroprotective and Neurite Outgrowth Enhancing Activities from Magnolia liliiflora.

Three rare spirocyclohexadienone-type neolignans, magnoflorins A-C (1-3), and three known analogs (4-6), were isolated from the leaves of Magnolia liliiflora. Magnoflorin D (4) was obtained from natural resources for the first time. The chemical structures and absolute configurations of 1-4 were elucidated through detailed analysis of HR-ESI-MS, IR, 1 H, 13 C, and 2D NMR, and ECD experiments. The absolute configuration of 5 were characterized by X-ray crystallography in present study. Moreover, compounds 4 and 5 displayed moderate neuroprotective activity against corticosterone-induced PC12 cells injury at 20 µM with cell viability of 71.5±0.99 % and 73.0±1.42 %, respectively, compared to the model group with 60.83±0.93 %. Compound 6 could enhance neurite outgrowth of nerve growth factor (NGF)-induced PC12 cells at 10 µM with the differentiation rate of 11.98 %, compared with 20.49 % of 50 ng/ml NGF.

Four Highly Oxygenated Sesquiterpenoids from the Fruits of Illicium micranthum Dunn.

Four highly oxygenated sesquiterpenoids, illimicranolides A (1) and B (2), and illicinolides E (3) and F (4), were obtained from the fruits of Illicium micranthum Dunn, as well as one known analog, illicinolide B (5). The chemical structures of 1-4 were determined comprehensively by 1D (1 H and 13 C) and 2D (HMBC, HSQC, 1 H-1 H COSY, and ROESY) NMR, and HR-ESI-MS data. Structurally, compound 1 was an unprecedented sesquiterpenoid with a 5/5/6/5-fused tetracyclic ring system and was the first seco-prezizaane sesquiterpenoid featuring a 11,8-γ-lactone ring. Compounds 3 and 4 were the fifth and sixth examples of illicinolide-type sesquiterpenoids. Moreover, compound 1 demonstrated neurotrophic activity of NGF-induced PC12 cells with differentiation rate of 10.34 % at a concentration of 10 µM.

Hypopurolides A - G, Labdane Diterpenoids from Hypoestes purpurea and Their Nitric Oxide Inhibitory Activity.

Seven new labdane diterpenoids, hypopurolides A-G (1-7) were discovered from the aerial part of Hypoestes purpurea, along with one known analog, hypopurin D (8). The structures of 1-7 were characterized based on 1 H-, 13 C-, and 2D-NMR, and HR-ESI-MS spectra. The absolute configurations of 1-7 were defined by single-crystal X-ray diffraction and electronic circular dichroism (ECD) data. Compounds 1-8 were tested for their nitric oxide (NO) inhibitory and cytotoxic effects. Compound 6 displayed moderate inhibitory effect toward LPS-induced NO release in RAW 264.7 cells with an IC50 value of 41.50 µM.

seco-Prezizanne Sesquiterpenes and Prenylated C6-C3 Compounds from the Fruits of Illicium lanceolatum A. C. Smith.

Two new seco-prezizaane-type sesquiterpenes, 2ß-hydroxy-6-deoxyneoanisatin (1) and 3,4-anhydro-2-oxo-1α-hydroxy-6-deoxyneoanisatin (2), and two new prenylated C6 -C3 compounds, illilanceofunones A (3) and B (4), were obtained from the fruits of Illicium lanceolatum, along with four known prenylated C6 -C3 compounds (5-8). Their structures were proposed through HR-ESI-MS, 1 H, 13 C, and 2D NMR data interpretation. Moreover, the absolute configuration of 1 and 2 were further assigned by single-crystal X-ray diffraction analysis and electronic circular dichroism (ECD) calculations, respectively. Illihenryipyranol A (6) exhibited neuroprotective activity against MPP+ -induced PC12 cell damage in a dose-dependent manner.

Cassane diterpenoids from the seeds of Caesalpinia bonduc and their nitric oxide production and α-glucosidase inhibitory activities.

Ten previously undescribed cassane diterpenoids, cassabonducins A-J, and eleven known compounds were isolated from the seeds of Caesalpinia bonduc. The structures of the undescribed compounds were elucidated by extensive analysis of spectroscopic data (IR, HRESIMS, and 1H, 13C and 2D NMR) and their absolute configurations were determined by the ECD data and single-crystal X-ray diffraction analysis. ε-Caesalpin-Ⅶ was obtained from natural resources for the first time. Cassabonducin A possessed noteworthy inhibitory activity against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages with IC50 value of 6.12 µM. Cassabonducin D and neocaesalpin N showed moderate α-glucosidase inhibition at the concentration of 50 µM with inhibitory capacities of 47.17% and 43.83%, respectively.

Synthesis of pterodontic acid derivatives and the study of their anti-influenza A virus (H1N1) activity.

Laggera pterodonta (DC.) Benth, a folk herb widely distributes in southwest China, especially in Yunnan Province, demonstrates anti-pathogenic microorganisms, anti-inflammatory, inhibition of Helicobacter pylori activities in vitro et al. Interestingly, previous studies have shown that pterodontic acid (1), a eudesmane-type sesquiterpene isolated from L. pterodonta (DC.), displays excellent selective antiviral activity to H1N1 subtype of influenza A virus. At the same time, our group also discovered that the antiviral activity of 1 was relatively close to that activity of post-marketed ribavirin. Therefore, we consider that the synthesis of pterodontic acid (1) derivatives and evaluation of their anti-influenza A virus (H1N1) activities is of potential clinical significance. In this manuscript, a series of pterodontic acid derivatives were prepared and demonstrated significantly improved anti-influenza A virus (H1N1) activities, providing more opportunities for the treatment of respiratory viral diseases.

Mangiferin promotes intestinal elimination of uric acid by modulating intestinal transporters.

Increasing evidence shows that the intestinal tract plays an important role in maintaining urate homeostasis and might be a potential therapeutic target for hyperuricaemia. However, uric acid-lowering drugs available in the clinic do not target intestinal excretion as a therapeutic strategy. We previously reported that mangiferin had potent hypouricaemic effects in hyperuricaemic animals. However, the underlying mechanisms are not completely clear. Here, we investigated the effects of mangiferin on the intestinal excretion of urate and its underlying mechanisms. The data revealed that mangiferin concentration-dependently promoted the intestinal secretion of endogenous urate in in situ intestinal closed loops in normal and hyperuricaemic mice, as well as inhibited the absorption of exogenous uric acid perfused into the intestinal loops in rats. Administration of mangiferin not only decreased the serum urate levels in the hyperuricaemic mice but also increased the protein expression of ATP-binding cassette transporter, subfamily G, member 2 (ABCG2) and inhibited the protein expression of glucose transporter 9 (GLUT 9) in the intestine. These findings suggested that intestinal ABCG2 and GLUT9 might be pivotal and possible action sites for the observed hypouricaemic effects. Moreover, no significant changes in intestinal xanthine oxidoreductase activities were observed, suggesting that mangiferin did not affect intestinal uric acid generation in the hyperuricaemic mice. Overall, promoting intestinal elimination of urate by upregulating ABCG2 expression and downregulating GLUT9 expression might be an important mechanism underlying mangiferin lowering serum uric acid levels. Mangiferin supplementation might be beneficial for the prevention and treatment of hyperuricaemia.

Caesalpanins A-C, Three Dimeric Cassane Diterpenoids from the Seeds of Caesalpinia sappan L.

Three dimeric cassane diterpenoids, caesalpanins A-C, were isolated from the seeds of Caesalpinia sappan L., as well as three known compounds. Their structures were determined via analysis of 1D-, 2D-NMR, and HR-ESI-MS data. Caesalpanins A and B were the second and third compounds that presented a nitrogen-containing cassane diterpenoid dimer linked through one ether bond between C-19 and C-20'. Caesalpanin B exhibited moderate cytotoxic activity against MCF-7 cell lines with IC50 value of 29.98 µm. Caesalpanins A and B had weak inhibitory effects against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages at 50 µm with inhibitory rate of 36.01 % and 32.93 %, respectively.

New azaphilones from Penicillium variabile, a fungal endophyte from roots of Aconitum vilmorinianum.

Two new azaphilone derivatives, comazaphilones G and H (1 and 2), together with eight known analogues (3-10), were isolated from an endophytic fungus Penicillium variabile. Their structures were established on the basis of extensive spectroscopic analysis. Compounds 1, 2 and 4-10 were tested their nitric oxide inhibitory activities in lipopolysaccharide-activated RAW 264.7 macrophage cells. Compounds 1, 2 and 4-9 showed significant nitric oxide inhibitory activities with IC50 values ranged from 4.35 ± 0.05 to 40.52 ± 0.47 µM.

Diterpenoids and sesquiterpenoids from the stem bark of Metasequoia glyptostroboides.

A phytochemical study on the stem bark of Metasequoia glyptostroboides led to the isolation of sixty-one diterpenoids and sesquiterpenoids, including seventeen previously undescribed compounds, metaglyptins A-Q. Their structures were elucidated by extensive analysis of spectroscopic data (IR, UV, HRESIMS, and 1H, 13C and 2D NMR). The absolute configurations of metaglyptins I, J, and O were determined by the ECD data and single-crystal X-ray diffraction analysis. The undescribed compounds were evaluated for their cytotoxicity against HeLa, AGS, and MDA-MB-231 cancer cell lines. The results revealed that metaglyptin A exhibited moderate cytotoxicity against MDA-MB-231 cell line with IC50 value of 20.02 µM.

Sesquiterpenes from the Leaves of Magnolia delavayi Franch. and Their Cytotoxic Activities.

Thirteen sesquiterpenes including eight new ones, magnodelavins A-H (1-8), were obtained from the 95 % ethanolic extract of the leaves of Magnolia delavayi Franch. The structures of the new compounds were determined by exhaustive 1 H-, 13 C-, 2D-NMR, UV, IR, and HR-ESI-MS data, as well as X-ray crystallographic analysis. Compounds 9 and 10 showed potent cytotoxic activities against HL-60, A-549, SMMC-7721, MCF-7, and SW480 human cancer cell lines in vitro using MTS assay.

Cytotoxic sesquiterpenoids from the leaves of Magnolia grandiflora.

Nine previously undescribed sesquiterpenoids, named magnograndins A-I, as well as fourteen known ones, were obtained from the 70% acetone extract of the leaves of Magnolia grandiflora. Their structures were ascertained based on the spectroscopic evidences. The assignment of the relative configuration of magnograndin A was further confirmed by single-crystal X-ray diffraction analysis. 1ß,10α-Epoxyparthenolide, parthenolide, and micheliolide exhibited potent cytotoxic activity against MDA-MB-468, AGS, HCT116, Hela, and MDA-MB-231 human cancer cell lines with IC50 values ranging from 1.76 to 16.11 µM. 1ß,10α-Epoxyparthenolide and micheliolide potently inhibited NF-κB transcriptional activity with IC50 of 13.92 and 8.95 µM, respectively. The expression levels of NF-κB downstream protein p65 and XIAP were clearly down-regulated in 1ß,10α-epoxyparthenolide and micheliolide treated cells, which demonstrated the inhibition of NF-κB signaling pathway.

Hypofolins A - L, ent-Labdane Diterpenoids from the Roots of Hypoestes phyllostachya 'Pink Splash'.

Twelve new ent-labdane diterpenoids, hypofolins A - F (1 - 6) and hypofolins G - L (7a/7b, 8a/8b, and 9a/9b), were isolated from the roots of Hypoestes phyllostachya 'Pink Splash'. Their structures were elucidated by extensive 1D- and 2D-NMR spectroscopic and HR-MS data. The absolute configurations of 1, 2, 5, and 7a/7b were determined by single crystal X-ray diffraction and ECD analysis, as well as chemical transformations. Compounds 7a/7b, 8a/8b, and 9a/9b were isolated as three pairs of interconverting mixture of two isomers between ketone and hemiketal types. Compound 1 showed weak cytotoxicity against SMMC-7721 cell line with IC50 value of 31.40 µm.

[A new cassane diterpene from Caesalpinia bonduc].

Five cassane diterpenes were isolated from the 95% ethanol extract of the seeds of Caesalpinia bonduc (Leguminosea) by a combination of various chromatographic methods, including silica gel, Sephadex LH-20, and semi-preparative HPLC. On the basis of spectroscopic techniques, their structures were identified as 3ß-acetoxy-cassa-12,14(17),15-trien-7ß-ol (1), caesalmin C (2), caesall E (3), caesalpinin MJ (4), and 1-deacetylcaesalmin C (5). Among them, compound 1 is a new compound and 2, 4, 5 were isolated from the plant for the first time.

[Chemical Constituents of Inula japonica].

Objective: To study the chemical constituents of Inula japonica. Methods: Silica gel, Sephadex LH-20,MCI and semipreparative HPLC were used to isolate and purify the constituents of Inula japonica,and the chemical structures were elucidated by chemical properties, MS and NMR analysis. Results: 14 compounds were isolated and their structures were identified as ivangustin( 1),1-acetoxy-6α-hydroxyeriolanolide( 2), 1ß-hydroxyalantolactone( 3),tomentosin( 4),11,13-dihydroinuchinenolide B( 5), britanlin A( 6),vomifoliol( 7), 17-hydroxy-16α-ent-kauran-19-oic acid( 8), 12-hydroxygeranylgeraniol ( 9), dihydroquercetin( 10), kaempferol( 11), quercetin( 12), dihydroconiferyl alcohol( 13) and fareanol( 14). Conclusion: Compounds 5,6,9,13 and 14 are isolated from this plant for the first time.

[Chemical constituents of Eucommia ulmoides].

OBJECTIVE: To study the chemical compositions of Eucommia ulmoides. METHODS: The compounds were isolated and purified from Eucommia ulmoides by silica gel column chromatography, Sephadex LH-20, MPLC packed with MCI gel and semi-preparative HPLC. The structures of these compounds were established on the basis of spectral analyses (1H-NMR, 13C-NMR and MS). RESULTS: Thirteen compounds were obtained,and their structures were identified as betulin (1), syringin (2), pervoside A (3), glucosyringic acid (4), vanillic acid-beta-glucoside (5), geniposide acid (6), aucubin (7), geniposide (8), pinoresinol-4,4'-di-O-beta-D-glucopyranoside (9), syringaresinol di-O-beta-D-glucopyranoside (10), medioresinol di-O-beta-D-glucopyranoside (11), sucrose (12), and ethyl beta-glucopyranoside (13) on the basis of physical characteristics and spectral data. CONCLUSION: Compounds 3 - 5, 12 and 13 are isolated from this plant for the first itme.

Triterpenoids and steroids with cytotoxic activity from Emmenopterys henryi.

Two new ursane-type triterpenoids, 3ß,19α,23-trihydroxyurs-12-en-24-al-28-oic acid (1) and 3ß,19α,24-trihydroxy-23-norurs-12-en-28-oic acid (2), two new pregnane derivatives, 3ß,12ß-dihydroxy-5α-pregnane-14,16-dien-20-one (9) and 12ß-hydroxy-5α-pregnane-14,16-dien-3,20-dione (10), and eight known compounds were isolated from the twigs and leaves of Emmenopterys henryi. The structures of the new compounds were elucidated on the basis of extensive spectroscopic analysis, including 1D and 2D NMR experiments. Compounds 4, 11, and 12 showed cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW-480 cell lines with IC50 values in the range of 3.11-20.12 µM.

Diterpenoids from the twigs and leaves of Fokienia hodginsii.

Five new isopimarane diterpenoids, fokihodgins A-E (1-5), four new labdane diterpenoids, fokihodgins F-I (6-9), and one new icetexane diterpenoid, fokihodgin J (10), as well as 18 known diterpenoids were isolated from Fokienia hodginsii. The structures of the new compounds were determined on the basis of their spectroscopic analysis, and the absolute configurations of 1 and 6 were established by X-ray crystallographic analysis. Compound 9 showed moderate cytotoxicity against HL-60 and SMMC-7721 cell lines, with IC50 values of 9.10 and 7.50 µM, respectively.