Four New Flavonoids with α‐Glucosidase Inhibitory Activities from Morus alba var. tatarica

Four new flavonoids, mortatarins A–D ( 1 – 4 , resp.), along with eight known flavonoids ( 5 – 12 ) were isolated from the root bark of Morus alba var. tatarica. Their structures were established on the basis of spectroscopic data analysis, and the absolute configuration of 4 was determined by analysis of its CD spectrum. All isolates were tested for inhibitory activities against α‐glucosidase. Compounds 4, 7 , and 8 exhibited a significant degree of inhibition with IC₅₀ values of 5.0±0.3, 7.5±0.5, and 5.9±0.2 μM , respectively.     

Isoquinoline Alkaloids from Fumaria officinalis L. and Their Biological Activities Related to Alzheimer's Disease

Two new isoquinoline alkaloids, named fumaranine ( 2 ) and fumarostrejdine ( 10 ), along with 18 known alkaloids were isolated from aerial parts of Fumaria officinalis. The structures of the isolated compounds were elucidated on the basis of spectroscopic analyses and by comparison with literature data. The absolute configuration of the new compound 2 was determined by comparing its circular dichroism spectra with those of known analogs. Compounds isolated in sufficient amounts were evaluated for their acetylcholinesterase, butyrylcholinesterase, prolyl oligopeptidase (POP), and glycogen synthase kinase‐3β inhibitory activities. Parfumidine ( 8 ) and sinactine ( 15 ) exhibited potent POP inhibition activities (IC₅₀ 99±5 and 53±2 μM , resp.).     

New Spirostane from a Fungus Neohelicomyces hyalosporus and Its Bioactivity

A new spirostane, namely neohelicomyine B ( 1 ), together with six known steroids ( 2 – 7 ) were isolated from the fermentation of fungus Neohelicomyces hyalosporus. The structures of these compounds were elucidated by extensive analyses of spectroscopic methods including 1D and 2D NMR and HR-ESI-MS. The absolute configuration of 1 was confirmed by single-crystal X-ray diffraction. The bioactivities of compounds 1 – 7 were evaluated using cellular assays. Compound 1 displayed moderate cytotoxicity against HepG2 cells (hepatoma cells) with IC₅₀ value of 8.4±2.1 μM. Compound 7 also exhibited cytotoxic activity against HepG2 cells with the IC₅₀ value of 3.0±0.2 μM.     

Westalsan: A New Acetylcholine Esterase Inhibitor from the Endophytic Fungus Westerdykella nigra

A new cytochalasan alkaloid, westalsan ( 1 ), along with two known cytochalasan compounds, phomacin B ( 2 ) and 19-hydroxy-19,20-dihydrophomacin C ( 3 ), were isolated from the solid rice culture of Westerdykella nigra, a marine-derived endophytic fungus, isolated from the roots of mangrove Avicennia marina (Forssk.) Vierh. The structures of compounds 1 – 3 were established on the basis of extensive 1D and 2D NMR spectroscopic techniques in combination with HR-ESI-MS. The ability of the isolated compounds to inhibit acetylcholine esterase activity was evaluated. Compound 3 showed the highest acetylcholine esterase inhibitory activity (IC₅₀ 0.056±0.003 μM), followed by compound 1 (IC₅₀ 0.088±0.005 μM) and compound 2 (IC₅₀ 0.140±0.007 μM) compared to donepezil (IC₅₀ 0.035±0.002 μM). This was further confirmed by molecular docking experiment.     

Isolation,Stereochemical Study,and Antioxidant Activity of Benzofuranone Derivatives from a Mangrove‐derived Fungus Eurotium rubrum MA‐150

Enantiomers of a 2‐benzofuran‐1(3H)‐one derivative [(–)‐ 1 and (+)‐ 1 ] and four known analogs ( 2 , 3 , 4 , 5 ) were isolated and identified from the culture extract of Eurotium rubrum MA–150, a fungus obtained from the mangrove‐derived rizospheric soil. Their structures were established by detailed interpretation of nuclear magnetic resonance (NMR) data and the structure of (±)‐ 1 was confirmed by single‐crystal X‐ray diffraction analysis. The absolute configuration of the enantiomers (–)‐ 1 and (+)‐ 1 was determined by means of online high‐performance liquid chromatography – electronic circular dichroism (HPLC‐ECD) measurements and time‐dependent Density Functional Theory – electronic circular dichroism (TDDFT‐ECD) calculations. Compounds (±)‐ 1 as well as 2 and 3 exhibited potent DPPH radical scavenging activities with IC₅₀ values of 1.23, 2.26, and 3.99 μg/mL, respectively. Chirality 28:581–584, 2016. © 2016 Wiley Periodicals, Inc.     

Antiviral Triketone‐Phloroglucinol‐Monoterpene Adducts from Callistemon rigidus

Callistrilones F – K ( 1 – 6 ), six new triketone‐phloroglucinol‐monoterpene hybrids were isolated from the twigs and leaves of Callistemon rigidus. Their structures with absolute configurations were established by a combination analysis of NMR spectra, X‐ray diffraction, and electronic circular dichroism (ECD) calculations. Compounds 3 and 4 exhibited moderate inhibitory activities against herpes simplex virus (HSV‐1) with IC₅₀ values of 10.00 ± 2.50 and 12.50 ± 1.30 μm , respectively.     

Five New Oleanane Triterpene Saponins from Camellia petelotii and Their Alpha-glucosidase Inhibitory Activity

Five new triterpenoid glycosides, named campetelosides A–E ( 1–5 ), together with three known compounds, chikusetsusaponin IVa ( 6 ), umbellatoside B ( 7 ), and silvioside E ( 8 ) were isolated from the leaves of Camellia petelotii (Merr.) Sealy. Their chemical structures were determined by interpretations of HR-ESI-MS and NMR spectra. In addition, compounds 1–8 were evaluated for their α-glucosidase inhibitory effects. Compounds 1–3 significantly showed α-glucosidase inhibitory activity with IC₅₀ values of 166.7±6.0, 45.9±2.6, and 395.3±10.5 μM, respectively, compared to that of the positive control, acarbose, with an IC₅₀ value of 200.4±10.5 μM.     

Nitric Oxide Production Inhibitory Eudesmane‐Type Sesquiterpenoids from Artemisia argyi

Six new eudesmane‐type sesquiterpene derivatives, artemargyinins A–F were isolated from the leaves of Artemisia argyi. Their structures were elucidated based on the extensive analysis of spectroscopic data. Artemargyinins A–F feature a lactone ring‐opening eudesmane‐type sesquiterpene with an isoprenoid group at C(8). All compounds were tested for their inhibitory effects on lipopolysaccharide‐induced nitric oxide (NO) production in RAW264.7 macrophages. Artemargyinins A–F showed more potent NO production inhibitory activity with IC₅₀ values ranging from 7.66±0.53 to 61.19±2.54 μM than the positive control quercetin (IC₅₀=74.34±1.39 μM). Among them, artemargyinins C and D exhibited strong inhibitory activity with IC₅₀ values of 8.08±0.21 and 7.66±0.53 μM, respectively.     

Two New Eudesmane-Type Sesquiterpene from Clonostachys sp. Y6-1and Their Cytotoxic Activity

Two undescribed eudesmane-type sesquiterpenoids together with four known compounds were isolated from Clonostachys sp. Y6-1 associated. Their chemical structures were unambiguously determined by NMR, mass spectrometry, and ¹³C-NMR calculation as well as DP4+ probability analyses. The absolute configurations of compounds 1 and 2 were determined by ECD calculation and X-ray single-crystal diffraction methods. Furthermore, all isolates were evaluated for in vitro cytotoxic activities against MCF-7, HCT-116, MDA-MB-231, and SW620 cancer cells. Among them, bioactivity evaluation of compound 5 revealed that weak activity (IC₅₀=66.55±0.82 μM) against SW620.     

New Isopropyl Chromone and Flavanone Glucoside Compounds from the Leaves of Syzygium cerasiforme (Blume) Merr. & L.M.Perry and Their Inhibition of Nitric Oxide Production

A new isopropyl chromone ( 1 ) and a new flavanone glucoside ( 2 ) together with eleven known compounds ( 3–13 ) were isolated from the leaves of Syzygium cerasiforme (Blume) Merr. & L.M.Perry. Their structures were elucidated as 5,7-dihydroxy-2-isopropyl-6,8-dimethyl-4H-chromen-4-one ( 1 ), 5,7-dihydroxyflavanone 7-O-β-D-(6′′-O-galloylglucopyranoside) ( 2 ), strobopinin ( 3 ), demethoxymatteucinol ( 4 ), pinocembrin-7-O-β-D-glucopyranoside ( 5 ), (2S)-hydroxynaringenin-7-O-β-D-glucopyranoside ( 6 ), afzelin ( 7 ), quercetin ( 8 ), kaplanin ( 9 ), endoperoxide G3 ( 10 ), grasshopper ( 11 ), vomifoliol ( 12 ), litseagermacrane ( 13 ) by the analysis of HR-ESI-MS, NMR, and CD spectral data. Compounds 1 , 2 , 5 , 6 and 10 inhibited NO production on LPS-activated RAW264.7 cells with IC₅₀ values of 12.28±1.15, 8.52±1.62, 7.68±0.87, 9.67±0.57, and 6.69±0.34 μM, respectively, while the IC₅₀ values of the other compounds ranging from 33.38±0.78 to 86.51±2.98 μM, compared to that of the positive control, N^G-monomethyl-L-arginine acetate (L-NMMA) with an IC₅₀ value of 32.50±1.00 μM.     

Bioactive scalemic caged xanthones from the leaves of Garcinia bracteata

Four pairs of previously undescribed caged xanthones (1–4) and twelve known caged xanthones (5–16) were isolated from the leaf extract of Garcinia bracteata. Their structures were unambiguously elucidated on the basis of spectroscopic methods. The planar structure and relative configuration of 1 was confirmed by X-ray crystallographic analysis. The enantiomers of compounds 1, 2, 4 were further resolved by semi-preparative chiral HPLC, and the absolute configurations of enantiomers of compounds 1 and 4 were determined by measurement and calculation of electronic circular dichroism (ECD) spectra and specific rotations. The inhibitory activities of the isolated compounds against human HeLa, A549, PC-3, HT-29, and WPMY-1 cell lines were assayed, and garcibractatin A (4) showed the most potent inhibitory activities in vitro with IC₅₀ values from 1.11 to 2.93 μM. A preliminary structure-activity relationship has been discussed, and some helpful conclusions have been drawn.     

Hypoglycemic activity of the antioxidant saponarin,characterized as α-glucosidase inhibitor present in Tinospora cordifolia

Tinospora cordifolia, used in anti-diabetic herbal drug preparations, was reported [12] to contain an α-glucosidase inhibitor, characterized as saponarin (apigenin-6-C-glucosyl-7-O-glucoside). The leaf extract had appreciable antioxidant and hydroxyl radical scavenging activities and contained the flavonoid in the range of 32.1 ± 1.5–45.5 ± 3.5 mg/g of dry solid. Saponarin showed mixed competitive inhibition on activities of α-glucosidase and sucrase of different origins. IC₅₀, Ki and ki′ values determined were 48 μM, 8 μM and 19.5 μM respectively for intestinal maltase and 35 μM, 6 μM and 13 μM respectively for intestinal sucrase. When given orally to maltose-fed rat, saponarin showed hypoglycemic activity in the range of 20–80 mg/kg compared to 100–200 mg/kg for acarbose as reported [27].     

Four New Cryptoporic Acid Derivatives from the Fruiting Bodies of Cryptoporus sinensis,and Their Inhibitory Effects on Nitric Oxide Production

Four new drimane‐type sesquiterpenoid ethers of isocitric acid, named cryptoporic acids J–M, were isolated from the fruiting bodies of Cryptoporus sinensis, together with six known cryptoporic acids. Their structures were elucidated on the basis of extensive spectroscopic analyses. Among them, cryptoporic acid D showed strong inhibition against nitric oxide (NO) production in macrophages with an IC₅₀ of 45.8±3.6 μM , comparable to the positive control of hydrocortisone (IC₅₀ of 40.6±2.5 μM ).     

Tetranorlanostane and Lanostane Triterpenoids with Cytotoxic Activity from the Epidermis of Poria cocos

Two unprecedented tetranorlanostane triterpenoids, poricolides A ( 1 ) and B ( 2 ), and two new lanostane triterpenoids, 3β-acetoxy-24-methyllanosta-8,16,24(31)-trien-21-oic acid ( 3 ) and 3β-acetoxylanosta-7,9(11),16,23-tetraen-21-oic acid ( 4 ), were isolated from the epidermis of Poria cocos. The structures of 1–4 were determined via analysis of ¹H-, ¹³C-, and 2D-NMR, and HR-ESI-MS data, and the absolute configurations of 1 and 3 were established by single-crystal X-ray diffraction analysis. Compounds 1 and 2 were the first report of tetranorlanostane triterpenoid having a δ-lactone ring at C(17). Compounds 3 and 4 were rare lanostane triterpenoids having a double bond between C(16) and C(17). Compounds 1–4 exhibited potent antiproliferative effects against A549, SMMC-7721, MCF-7, and SW480 cancer cell lines with IC₅₀ values from 16.19±0.38 to 27.74±1.12 μM.     

Two new resveratrol tetramers isolated from Cayratia japonica (Thunb.) Gagn. with strong inhibitory activity on fatty acid synthase and antioxidant activity

Two new resveratrol tetramers, cajyphenol A ( 1 ) and cajyphenol B ( 2 ), together with two known resveratrol dimers, quadrangularin A ( 3 ) and pallidol ( 4 ), and resveratrol ( 5 ) were isolated from the stems of Cayratia japonica (Thunb. ) Gagn. Their structures were established by means of NMR (¹H,¹H‐COSY, ¹H,¹³C‐HSQC, HMBC, and NOESY) and ESI‐MS analyses. Compounds 1 – 5 showed fast‐binding inhibitory activities on fatty acid synthase with the IC₅₀ values of 1.63±0.02, 1.49±0.03, 7.50±0.01, 11.1±0.01, and 10.2±0.01 μM , respectively. Compounds 1 – 5 also exhibited antioxidant activities in the ORAC assay.     

ent-Pimarane Diterpenes from the Aerial Parts of Siegesbeckia pubescens

Five new ent-pimarane diterpenes ( 1 – 5 ) and five known analogs ( 6 – 10 ) were isolated from the aerial parts of Siegesbeckia pubescens. Their structures, including absolute configurations, were determined by comprehensive spectroscopic methods especially 1D and 2D NMR and quantum chemical electronic circular dichroism calculations. All the isolated compounds were evaluated for their cytotoxicity against human BT549, A549 and H157 cancer cell lines. Among them, compounds 1 and 2 showed mild cytotoxicity against lung cancer cell lines H157 with IC₅₀ values of 16.35±2.59 and 18.86±4.83 μM, respectively.     

Urease inhibitors from Hypericum oblongifolium WALL.

The bioassay-guided fractionation of H. oblongifolium has led to the isolation of potent urease inhibitors 1–3. The structures were elucidated by NMR and mass spectroscopic techniques. Compound 2 showed a potent enzyme inhibition activity (IC₅₀ 20.96?±?0.93), which is comparatively higher than that for the standard thiourea (IC₅₀ 21.01?±?0.51 μM). Compounds 1 and 3 also showed a significant activity, with IC₅₀ 37.95?±?1.93 and 138.43?±?1.23 μM, respectively. The sub crude fractions (F1, F2, F3, and F4) were tested in vitro for their urease inhibition activity. Fractions F2 and F4 showed significant activity with IC₅₀ 140.37?±?1.93 and 167.43?±?3.03 μM, respectively.     

Phytoconstituents of Selaginella effusa Alston and Their α-Glucosidase as well as Urease Inhibitory Activities

Three new compounds ( 1 – 2 , 14 ), as well as 22 known compounds ( 3 – 13 , 15 – 25 ), were extracted for the first time from the Selaginella effusa Alston (S. effusa). For the unknown compounds, the planar configurations were determined via NMR and by high-resolution mass spectrometry, while their absolute configurations were determined by calculated electronic circular dichroism (ECD), and the configuration of the stereogenic center of biflavones 4 – 5 were established for the first time. The pure compounds ( 1 – 25 ) were tested in vitro to determine the inhibitory activity of the enzyme-catalyzed reactions. Compounds 1 – 9 inhibited α-glucosidase with IC₅₀ values ranging from 0.30±0.02 to 4.65±0.04 μM and kinetic analysis of enzyme inhibition indicated that biflavones 1 – 3 were mixed-type α-glucosidase inhibitors. Compounds 12 – 13 showed excellent inhibitory activity against urease, with compound 12 (IC₅₀=4.38±0.31 μM) showing better inhibitory activity than the positive control drug AHA (IC₅₀13.52±0.61 μM). In addition, molecular docking techniques were used to simulate inhibitor-enzyme binding and to estimate the binding posture of the α-glucosidase and urease catalytic sites.     

Pyrrole Derivatives and Diterpene Alkaloids from the South China Sea Sponge Agelas nakamurai

Two pairs of new non‐brominated racematic pyrrole derivatives, (±)‐nakamurine D ( 1 ) and (±)‐nakamurine E ( 2 ), two new diterpene alkaloids, isoagelasine C ( 16 ) and isoagelasidine B ( 21 ), together with 13 known pyrrole derivatives ((±)‐ 3  –  15 ), five known diterpene alkaloids ( 17  –  20 , 22 ) were isolated from the South China Sea sponge Agelas nakamurai . The racemic mixtures, compounds 1  –  4 , were resolved into four pairs of enantiomers, (+)‐ 1 and (?)‐ 1 , (+)‐ 2 and (?)‐ 2 , (+)‐ 3 and (?)‐ 3 , and (+)‐ 4 and (?)‐ 4 , by chiral HPLC . The structures and absolute configurations were elucidated on the basis of comprehensive spectroscopic analyses, quantum chemical calculations, quantitative measurements of molar rotations, application of van't Hoff 's principle of optical superposition, and comparison with the literature data. The NMR and MS data of compound 3 are reported for the first time, as the structure was listed in SciFinder Scholar with no associated reference. These non‐brominated pyrrole derivatives were found in this species for the first time. Compound 18 showed valuable cytotoxicities against HL ‐60, K562, and HCT ‐116 cell lines with IC ₅₀ values of 12.4, 16.0, and 19.8 μm , respectively. Compounds 16  –  19 , 21 , and 22 showed potent antifungal activities against Candida albicans with MIC values ranging from 0.59 to 4.69 μg/ml. Compounds 16  –  19 exhibited moderate antibacterial activities against Proteusbacillus vulgaris (MIC values ranging from 9.38 to 18.75 μg/ml).     

Benzophenones from Guignardia sp. IFB‐E028, an Endophyte on Hopea hainanensis

The first natural S‐containing benzophenone dimer, named guignasulfide ( 3 ), was isolated from the culture of Guignardia sp. IFB‐E028, an endophytic fungus residing in healthy leaves of Hopea hainanensis. Its structure was determined through correlative analyses of its MS, 1D‐ and 2D‐NMR spectroscopic data. Two other known benzophenone derivatives, monomethylsulochrin and rhizoctonic acid ( 1 and 2 , resp.) were also isolated. Guignasulfide ( 3 ) was more active against the human liver cancer cell line HepG2 (IC₅₀ value: 5.2±0.4 μM ) than metabolites 1 and 2 (IC₅₀ values: 63.5±0.6 and 60.2±0.5 μM ); compounds 1 – 3 showed also moderately inhibitory effects on the human bacterial pathogen Helicobacter pylori with MIC values of 28.9±0.1, 60.2±0.4, and 42.9±0.5 μM , respectively.