Anti-inflammatory sesquiterpene lactones from the flower of Vernonia cinerea

Bioassay-guided fractionation of the hexane extract from the flowers of Vernonia cinerea (Asteraceae) led to the isolation of a new sesquiterpene lactone, 8α-hydroxyhirsutinolide (2), and a new naturally occurring derivative, 8α-hydroxyl-1-O-methylhirsutinolide (3), along with seven known compounds (1 and 4-9). The structures of the new compounds were determined by 1D and 2D NMR experiments and by comparison with the structure of compound 1, whose relative stereochemistry was determined by X-ray analysis. The isolated compounds were evaluated for their cancer chemopreventive potential based on their ability to inhibit nitric oxide (NO) production and tumor necrosis factor alpha (TNF-α)-induced NF-κB activity. Compounds 1, 2, 4, 5, and 9 inhibited TNF-α-induced NF-κB activity with IC(50) values of 3.1, 1.9, 0.6, 5.2, and 1.6μM, respectively; compounds 4 and 6-9 exhibited significant NO inhibitory activity with IC(50) values of 2.0, 1.5, 1.2, 2.7, and 2.4μM, respectively.     

Chemical Constituents from the Stems of Excoecaria acertiflia

Six new compounds, including two diterpenoids excocarinols F and G ( 1 and 2 , resp.), two carotane (daucane) sesquiterpenoids excoecafolinols A and B ( 3 and 4 , resp.), one lignanoid compound, excoecanol A ( 5 ), and one simple phenol, excoecanol B ( 6 ), together with 17 known compounds, were isolated from the BuOH extract of Excoecaria acerifolia Didr . stems. Their structures were elucidated through the analysis of the spectroscopic data. The AChE‐inhibitory activities of 17 compounds were evaluated and revealed that four of them possessed moderate inhibitory activities against AChE.     

Rhodomyrtosones G and H,minor phloroglucinols from the leaves of Rhodomyrtus tomentosa

Two new phloroglucinols named rhodomyrtosones G (1) and H (2) were isolated from the crude hexane extract of the leaves of Rhodomyrtus tomentosa along with three known compounds, rhodomyrtone (3), tomentosone B (4) and rhodomyrtosone C (5). Structural determination was carried out using conventional 1D and 2D NMR spectroscopic data and by comparing previously reported literatures as well.     

蛇足石杉内生真菌无柄盘菌Pezicula sp. JR14中抑制乙酰胆碱酯酶的次级代谢产物分离

采用形态学及ITS-rDNA序列分析法,对具有抑制乙酰胆碱酯酶活性的蛇足石杉内生菌株JR14进行鉴定,确定为无柄盘菌Pezicula sp.。开展了乙酰胆碱酯酶抑制活性化合物的分离,从Pezicula sp. JR14乙酸乙酯提取物中分离到4个化合物,利用核磁共振及质谱技术将其鉴定为behenic acid (1)、himeic acid B (2)、secalonic acid A (3)和palmitic acid (4)。采用改进的Ellman比色法对分离的化合物进行活性检测,结果表明,himeic acid B (2)具有较强的乙酰胆碱酯酶抑制活性,其IC₅₀为205μg/mL（0.64mmol/L）。     

Quinolinones Alkaloids with AChE Inhibitory Activity from Mangrove Endophytic Fungus Penicillium citrinum YX-002

Acetylcholinesterase (AChE) inhibitory activity-guided studies on the mangrove-derived endophytic fungus Penicillium citrinum YX-002 led to the isolation of nine secondary metabolites, including one new quinolinone derivative, quinolactone A ( 1 ), a pair of epimers quinolactacin C1 ( 2 ) and 3-epi-quinolactacin C1 ( 3 ), together with six known analogs ( 4 – 9 ). Their structures were elucidated based on extensive mass spectrometry (MS) and 1D/2D nuclear magnetic resonance (NMR) spectroscopic analyses, and compared with data in the literature. The absolute configurations of compounds 1 – 3 was determined by combination of electronic circular dichroism (ECD) calculations and X-Ray single crystal diffraction technique using CuK_α radiation. In bioassays, compounds 1 , 4 and 7 showed moderate AChE inhibitory activities with IC₅₀ values of 27.6, 19.4 and 11.2 μmol/L, respectively. The structure-activity relationships (SARs) analysis suggested that the existence of carbonyl group on C-3 and the oxygen atom on the five-membered ring were beneficial to the activity. Molecular docking results showed that compound 7 had a lower affinity interaction energy (−9.3 kcal/mol) with stronger interactions with different sites in AChE activities, which explained its higher activities.     

Leishmanicidal activities and cytotoxicities of bisnaphthoquinone analogues and naphthol derivatives from Burman Diospyros burmanica

A methanol extract of the wood of Diospyros burmanica, collected in Burma (Myanmar), was found to exhibit significant activity against Leishmania major. Subsequent chromatographically resolved fractionation led to the isolation of three novel bisnaphthoquinone analogues, burmanin A, B, and C (1-3), together with nine known compounds (4-12). The structure of 1 was confirmed by X-ray crystallography, and those of 2 and 3 by spectroscopic techniques, including 1D and 2D NMR. The inhibitory activities of the isolates were evaluated against the promastigote forms of Leishmania major and the murine macrophage-like cell line, RAW264.7.     

Antioxidative oligostilbenes from Caragana sinica

Two new oligostilbenes, caragasinins A (5) and B (10), and eight known compounds, kobophenol A (1), (+)-α-viniferin (2), (+)-ampelopsin F (3), pallidol (4), (+)-isoampelopsin F (6), miyabenol C (7), carasinaurone (8) and caraphenol B (9) were isolated from the ethylacetate-soluble extract of the roots of Caragana sinica. The structures of the isolates were determined on the basis of extensive spectroscopic analysis including 1D, 2D NMR and HRESI-MS. These compounds were assessed for antioxidant activities. Caragasinin A (5), caraphenol B (9), and caragasinin B (10) showed moderate DPPH scavenging activity and lipid peroxidation inhibitory activities with IC(50) values ranging from 34.7±1.0 to 89.1±2.3μM.     

Ecdysteroids from the flowers of Aerva javanica

Four new ecdysteroids (1–4), along with three known steroids, β-ecdysone (5), 5-β-2-deoxyintegristerone A (6) and 24-epi-makisterone A (7) (Fig. 1), were isolated from the methanolic extract of the flowers of Aerva javanica by using normal and reverse phase chromatography. The structures of the new compounds (1–4) were determined due to 1D (¹H and ¹³C), 2D NMR (HSQC, HMBC, COSY, NOESY) techniques and high resolution mass spectrometry (HREIMS). The known compounds (5–7) were characterized based on the 1D NMR spectroscopy and mass spectrometry and by comparison with the literature values. All isolates were evaluated for their inhibitory activities against enzymes acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and lipoxygenase (LOX).     

A new dimeric carbazole alkaloid from Murraya koenigii (L.) leaves with α-amylase and α-glucosidase inhibitory activities

A new dimeric carbazole alkaloid, 3,3′,5,5′,8-pentamethyl-3,3′-bis(4-methylpent-3-en-1-yl)-3,3′,11,11′-tetrahydro-10,10′-bipyrano[3,2-a]carbazole, was isolated from the hexane extract of leaves of Murraya koenigii (L.) Sprengel. (Family: Rutaceae). The structure was elucidated based on ¹³C and ¹H NMR, High-Resolution Mass Spectrometry (HRMS), and 2D NMR data. The in vitro antidiabetic activity of the new dimer was investigated in terms of α-amylase and α-glucosidase enzyme inhibition assays. The dimer exhibited significant α-amylase inhibitory activity (IC₅₀ = 30.32 ± 0.34 ppm) and α-glucosidase inhibitory activity (IC₅₀ = 30.91 ± 0.36 ppm).     

Four New Diterpenoid Alkaloids from The Roots of Aconitum coreanum

Four new hetisine‐type C₂₀‐diterpenoid alkaloids, named as coreanines A–D ( 1 – 4 ), were isolated from the roots of Aconitum coreanum, together with thirteen known alkaloids ( 5 – 17 ). Their structures were elucidated by extensive spectroscopic methods including IR, HR‐ESI‐MS and NMR techniques. All the isolated compounds were screened for the acetylcholinesterase (AChE) inhibitory effects, and none of them showed considerable inhibitory activity.     

Cholinesterase inhibitory and antioxidant properties of Verbascum mucronatum Lam. and its secondary metabolites

The aqueous extract of Verbascum mucronatum Lam. along with its fractions and secondary metabolites were assessed for their antioxidant, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory activities. The antioxidant activity was evaluated by three methods: as 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity, ferrous ion-chelating effect, and ferric-reducing antioxidant power (FRAP) tests. The AChE activity was determined by the Ellman method using an ELISA microplate reader. Phytochemical investigations revealed the presence of four iridoid glucosides, ajugol (1), aucubin (2), lasianthoside I (3) and catalpol (4), two saponins, ilwensisaponin A (5) and C (6), and a phenylethanoid glycoside, verbascoside (7), in Verbascum mucronatum. Their structures were elucidated by spectral techniques. The aqueous extract and fractions including the phenylethanoid glycoside 7 showed DPPH scavenger effect and had the best FRAP. Besides these results, one of the phenylethanoid fractions displayed the highest ferrous ion-chelating effect. While only 7 was found to possess moderate AChE inhibition, the extract, fractions, and all other tested compounds did not inhibit AChE and BChE.     

半枝莲抗肝癌活性部位的化学成分研究

前期研究发现,半枝莲(Scutellaria barbata)全草醇提物的乙酸乙酯萃取部位经大孔吸附树脂处理,其70%乙醇洗脱部位具有较好的抗肝癌活性。为明确其活性成分,该研究采用硅胶柱色谱、Sephadex LH-20柱色谱、制备TLC、半制备液相色谱等对活性部位进行分离和纯化,运用多种波谱分析方法鉴定了单体化合物结构,并利用CCK-8法评价了所有单体化合物对人肝癌HepG2细胞体外增殖抑制活性,同时利用分子对接技术考察了活性最好的化合物与肝癌靶标的结合情况。结果表明:(1)从该活性部位共分离得到14个化合物,包括12个新克罗烷型二萜类化合物和2个黄酮类化合物,分别鉴定为scutefolide C(1)、6-乙酰氧基-7-烟酸酰氧基半枝莲碱G(2)、scutestrigillosin D(3)、 scutehenanine D(4)、半枝莲碱A(5)、半枝莲碱B(6)、7-烟酸酰氧基半枝莲碱H(7)、半枝莲碱N(8)、半枝莲碱Y(9)、barbatin A(10)、barbatin B(11)、barbatin D(12)、5, 7, 6''-三羟基-2''-甲氧基黄酮醇(13)和5, 8-二羟基-6, 7-二甲氧基黄酮(14)。其中,化合物1-3、13、14为首次从该植物中分离得到。(2)活性测试结果显示,化合物4、7、10-12表现出较弱的HepG2细胞增殖抑制活性,化合物6的细胞增殖抑制活性和阳性对照(顺铂)活性接近,而化合物5表现出比顺铂更强的细胞增殖抑制活性。(3)分子对接结果显示,化合物5和化合物6与肝癌靶蛋白VEGF-2均具有良好的结合力。该研究结果不仅丰富了半枝莲的化学物质类群,也为进一步深入研究活性化合物抗肝癌的作用机制提供了参考。     

Ohioensins F and G: protein tyrosine phosphatase 1B inhibitory benzonaphthoxanthenones from the Antarctic moss Polytrichastrum alpinum

Ohioensins F and G (1 and 2), two new benzonaphthoxanthenones, have been isolated from the MeOH extract of Antarctic moss Polytrichastrum alpinum by various chromatographic methods. The structures of these compounds were determined mainly by analysis of NMR spectroscopic data. The known compounds ohioensins A and C (3 and 4) were also obtained. Compounds 1-4 showed potent inhibitory activity against therapeutically targeted protein tyrosine phosphatase 1B (PTP1B). Kinetic analysis of PTP1B inhibition by ohioensin F (1) suggested that benzonaphthoxanthenones inhibited PTP1B activity in a non-competitive manner.     

New ursane-type triterpenes from the root bark of Calotropis procera

As a part of our continuing interest in identifying anticancer drug leads from natural sources, we have investigated the in vitro growth inhibitory effects of the hexane fraction of the root bark of Calotropis procera (Ait) R. Br. (Asclepiadaceae). This study reports the isolation and structure elucidation of four new ursane-type triterpenes named calotroprocerol A (1), calotroproceryl acetate A (2), calotroprocerone A (3) and calotroproceryl acetate B (4) in addition to five known compounds including pseudo-taraxasterol acetate (5), taraxasterol (6), calotropursenyl acetate B (7), stigmasterol (8) and (E)-octadec-7-enoic acid (9). Their structures were established on the basis of 1D and 2D NMR studies (¹H–¹H COSY, HSQC, and HMBC) and HRMS spectral data. The in vitro growth inhibitory activity of the isolated compounds was evaluated against three human cancer cell lines including the A549 non-small cell lung cancer (NSCLC), the U373 glioblastoma (GBM) and the PC-3 prostate cancer cell lines.     

Insect growth regulator and insecticidal activity of beta-dihydroagarofurans from Maytenus spp. (Celastraceae)

From the aerial parts of Maytenus disticha, we have isolated 9beta-benzoyloxy-1alpha,2alpha,6beta,8alpha,15penta-acetoxy-dihydro-beta-agarofuran (1) and from seeds of Maytenus boaria 9beta-furoyloxy-1alpha,6beta,8alpha-triacetoxy-dihydro-beta-agarofuran (2). These compounds and their MeOH and hexane/ethyl acetate (1:1 v/v) extracts were evaluated for their effects on the fall armyworm (Spodoptera frugiperda). Toosendanin, a commercial insecticide derived from Melia azedarach was used as a positive control. When tested for activity using neonate larvae in a nochoice artificial diet bioassays, the agarofurans 1, 2 and toosendanin as well as the MeOH and hexane/EtOAc extracts caused significant growth inhibitory effects with GC50 of 7.55; 3.84; 1.75; 14.0 and 7.3 ppm at 7 days, respectively. Compounds 1 and 2 caused 100% larval mortality at 25 and 15 ppm, respectively. MeOH and hexane/EtOAc extracts caused 100% larval mortality at 25.0 ppm, respectively, they also increased the development time of surviving larvae and a significant delay for the time of pupation and adult emergence. These compounds showed comparable potency of activity with toosendanin. Acute toxicity against adults of S. frugiperda was also found, for hexane/EtOAc extract and 2 had the most potent activity with LD50 value of 4.7 and 1.9 ppm, respectively. MeOH extract, hexane/EtOAc extract, 1 and 2 caused acetylcholinesterase inhibition with 78.0, 89.2, 79.3 and 100% inhibition at 15.0 ppm, respectively. Therefore, the furoyloxy agarofuran may be responsible for the insecticidal activity of these plants.     

Constituents of the stems of Macrococculus pomiferus and their inhibitory activities against cyclooxygenases-1 and -2

As part of our program directed towards the discovery of new cancer chemopreventive agents from plants, the EtOAc-soluble extract of the stems of M. pomiferus was found to inhibit the enzyme cyclooxygenase-2 (COX-2). Bioassay-directed fractionation of this extract led to the isolation of two dibenzylbutyrolactone lignans, (8R,8'R)-3'-O-demethyl-5-hydroxymatairesinol (1) and (8R,8'R)-3'-O-demethyl-5-methoxymatairesinol (2), as well as seven known compounds, (-)-5'-methoxyyatein (3), blumenol A, (-)-deoxypodophyllotoxin (anthricin), (-)-deoxypodorhizone, 2,6-dimethoxyhydroquinone, 4-hydroxybenzaldehyde, and beta-sitosterol glucoside. The structures of compounds 1 and 2 were determined using spectroscopic data (1D and 2D NMR, and HREIMS), and the 8R and 8'R absolute stereochemistry was established for both 1 and 2 on the basis of their CD spectra. All isolates obtained in the present study were evaluated for their inhibitory effects with both COX-1 and -2. Of these, only 5'-methoxyyatein (3) showed weak activity against COX-2, while all other compounds isolated were inactive. The COX-2 inhibitory activity of the EtOAc extract was also traced to the presence of several common fatty acids by LC-MS.     

Cholinesterase inhibitory and spasmolytic potential of steroidal alkaloids

A new steroidal alkaloid, isosarcodine (1) along with four known bases, sarcorine (2), sarcodine (3), sarcocine (4) and alkaloid-C (5) were isolated from the MeOH extract of Sarcococca saligna. The structures of these alkaloids were identified by spectral data interpretation. These compounds were subjected to acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibition studies, and were found to be noncompetitive inhibitors of AChE (K_i = 21.8, 90.3, 32.2, 16.0 and 50.0 μM, respectively) and uncompetitive or noncompetitive inhibitors of BChE (K_i = 8.3, 7.5, 15.6, 5.0 and 12.0 μM, respectively).

The compounds (2–5) also showed dose-dependent spasmolytic activity in the rabbit jejunum intestinal preparations and also relaxed the high K⁺ (80 mM)-induced contraction, indicative of a calcium channel-blocking mechanism.

Structure–activity relationship suggested that the nitrogen substituents at C-3 and/or C-20 of steroidal skeleton and the hydrophobic properties of the pregnane skeleton are the key structural features contributed to the inhibitory potency of these steroidal alkaloids against AChE and BChE.     

黑蛞蝓化学成分研究(Ⅱ)

为研究中药材黑蛞蝓(Agriolimax agrestis)的化学成分及其化合物的α-糖苷酶抑制活性,本研究采用Sephadex LH-20、硅胶、Chromatorex C₁₈等柱色谱对黑蛞蝓正己烷提取物进行化学成分离纯化,通过NMR波谱数据与文献对比分析鉴定化合物结构。从黑蛞蝓正己烷提取物中共分离得到15个化合物,分别鉴定为苯乙醇(1)、十六烷酸(2)、(Z) 9-octadecenoic acid(3)、1-(2-hydroxyethoxy)ethyl (E)-octadec-9-enoate(4)、二十七烷(5)、dodecyl (Z)-9-hexadecenoate(6)、cis,cis-diunsaturated α-meromycolic acid(7)、1,2,3-propanetriyl (9Z,9′Z,9″Z)tris(-9-octadecenoate)(8)、胆固醇(9)、7-酮基胆固醇(10)、胆甾-5-烯-3β,7α二醇(11)、胆甾-5-烯-3β,7β二醇(12)、胆甾醇肉豆蔻酸酯(13)、胆甾醇基十七酸酯(14)、熊果酸(15)。除化...     

Prolyl endopeptidase inhibitors from Syzygium samarangense (Blume) Merr. & L. M. Perry

Compounds isolated from the hexane extract of the leaves of Syzygium samarangense (Blume) Merr. & L. M. Perry were tested for inhibitory activity against the following serine proteases: trypsin, thrombin and prolyl endopeptidase. The compounds were identified as an intractable mixture of alpha-carotene and beta-carotene (1), lupeol (2), betulin (3), epi-betulinic acid (4), 2',4'-dihydroxy-6'-methoxy-3'-methylchalcone (5), 2'-hydroxy-4',6'-dimethoxy-3'-methylchalcone (6), 2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone (7), 2',4'-dihydroxy-6'-methoxy-3'-methyldihydrochalcone (8) and 7-hydroxy-5-methoxy-6,8-dimethylflavanone (9). Hydrogenation of compounds 5, 6 and 7 yielded compound 8, 2'-hydroxy-4',6'-dimethoxy-3'-methyldihydrochalcone (10) and 2',4'-dihydroxy-6'-methoxy-3',5'-dimethyldihydrochalcone (11), respectively. The hydrogenated products of compounds 6 and 7 were also tested for enzyme inhibitory activity. In addition, beta-sitosterol (12) and beta-D-sitosterylglucoside (13) were also isolated. This is the first report of the isolation of compounds 1-6, 8 and 13 from this plant. Compounds 3-8 and 10 exhibited significant and selective inhibition against prolyl endopeptidase among three serine proteases. This is the first report of this kind of activity for all these compounds.     

Synthesis and biological activities of 2-oxocycloalkylsulfonamides

A series of novel 2-oxocycloalkylsulfonamides (4) were synthesized and their structures confirmed by IR, (1)H NMR, and elemental analysis. The bioassay showed that they have fair to excellent fungicidal activities against Botrytis cinerea Pers and Sclerotinia sclerotiorum. Among them, compounds 4A(10), 4A(11), 4A(12), 4B(2), and 4B(3), the EC(50) values of which were 2.12, 3.66, 3.96, 2.38, and 2.43 microg/mL, respectively, displayed excellent fungicidal activity against B. cinerea Pers, and are comparable with commercial fungicide procymidone (the EC(50) value is 2.45 microg/mL). 3D QSAR against B. cinerea Pers was studied, a statistically significant and chemically meaningful CoMFA model was developed and some compounds which have a high predicted activity were forecasted. In addition, the bioassay also showed that the compounds have good inhibitory activities against human tumor cells HL-60, BGC-823, Bel-7402 and KB. It is interesting to point out that the antitumor activities of compounds 4 are in accordance with their fungicidal activity to a great extent: compounds having relatively best antitumor activities (4A(10), 4A(11), 4A(12), and 4B(3)) also displayed excellent fungicidal activity.