New sugar-mimic alkaloids from the pods of Angylocalyx pynaertii

Chromatographic separation of the pod extract of Angylocalyx pynaertii resulted in the isolation of 13 sugar-mimic alkaloids (1-13). The structures of the new alkaloids were elucidated by spectroscopic methods as the 6-O-beta-D-glucoside (10) and N-hydroxyethyl derivative (11) of 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) (1), 1,6-dideoxynojirimycin (12), and 1,3,4-trideoxynojirimycin (13). 2,5-Imino-1,2,5-trideoxy-L-glucitol (7), 2,5-dideoxy-2,5-imino-D-fucitol (8), and beta-homofuconojirimycin (9), isolated from the pods as well as the bark, were very specific inhibitors of alpha-L-fucosidase with no significant inhibitory activity toward other glycosidases. In this work, 1,4-dideoxy-1,4-imino-D-ribitol (6) was found to be a better inhibitor of lysosomal beta-mannosidase than 2,5-imino-1,2,5-trideoxy-D-mannitol (2). N-Hydroxyethyl-1-deoxynojirimycin (miglitol), which is commercially available for the treatment of diabetes, retained its inhibitory potential toward rat intestinal maltase and sucrase, whereas 11 and the synthetic N-hydroxyethyl derivative of 2,5-dideoxy-2,5-imino-D-mannitol markedly lowered or abolished their inhibition toward all enzymes tested.     

A cytotoxic and antifungal 1,4-naphthoquinone and related compounds from a New Zealand brown algae, Landsburgia quercifolia.

The bioactivity-directed isolation of deoxylapachol [I] from a New Zealand brown alga, Landsburgia quercifolia, is described. Compound I was active against P-388 leukemia cells (IC50 0.6 microgm/ml) and was also antifungal. 1,4-Dimethoxy-2-(3-methyl-2-butenyl)-naphthalene [3] was the major low polarity component of extracts of this seaweed, which also contained 2,3-dihydro-2,2-bis(3-methyl-2-butenyl)-1,4-naphthalenedione [6] and 2-(3-methyl-2-butenyl)-2,3-epoxy- 1,4-naphthalenedione 4,4-dimethoxy ketal [7]. Compound 7 was converted to the 2,3-epoxide of I, which had biological activities similar to those of I.     

长穗桑中的α-葡萄糖苷酶抑制剂成分研究

 目的 研究长穗桑中具有α-葡萄糖苷酶抑制活性的化学成分。方法 采用各种离子交换树脂对长穗桑水提取物进行分离纯化,通过NMR、MS等波谱分析手段鉴定化合物结构。结果 从长穗桑水提取物中分离到11个化合物,其中7个多羟基生物碱类化合物,2个酰胺类化合物,1个氨基酸以及甜菜碱。分别鉴定为1-deoxynojirimycin (1),fagomine (2),3-epi-fagomine (3),1,4-dideoxy-1,4-imino-D-arabinitol (4),2-O-α-D-galactopyranosyl-1-deoxynojirimycin (5),4-O-β-D-glucopyranosyl-fagomine (6),1,4-dideoxy-1,4-imino-(2-O-β-D-glucopyranosyl)-D-arabinitol (7),(2S)-citrullinamide (8),grateloupinamide (9),天冬氨酸(10),甜菜碱(11)。化合物1~10分别进行了α-葡萄糖苷酶抑制活性筛选。结论 化合物1~11均为首次从该植物中分离得到。4个多羟基生物碱(1,5~7)以及1个酰胺类化合物(9)有较强的α-葡萄糖苷酶抑制活性,其中化合物1的IC₅₀为0.07 μmol·L^-1;化合物5的IC₅₀为0.39 μmol·L^-1,与阳性对照阿卡波糖(acarbose,IC₅₀=0.52 μmol·L^-1)相当;化合物6,7,9的IC₅₀值在1~5 μmol·L^-1。     

Iminosugar-producing Thai medicinal plants

Alpha-1-C-hydroxymethylfagomine (7), 3-O-beta-D-glucopyranosyl-DMDP (12), and 2,5-dideoxy-2,5-imino-D-glucitol (13) were isolated from the Thai traditional crude drug "Non tai yak" (Stemona tuberosa), which also contains a high concentration level of alpha-homonojirimycin (0.1% dry weight). "Thopthaep" (Connarus ferrugineus) and "Cha em thai" (Albizia myriophylla) contained 1-deoxymannojirimycin (DMJ) (10) at levels of 0.083% (dry weight) and 0.17% (dry weight), respectively. 2-O-alpha-D-Galactopyranosyl-DMJ (20), 3-O-beta-D-glucopyranosyl-DMJ (21), 1,4-dideoxymannojirimycin (17), 1,4-dideoxyallonojirimycin (18), and 1,4-dideoxyaltronojirimycin (19) from C. ferrugineus and 2-O-beta-D-glucopyranosyl-DMJ (22) and 4-O-beta-D-glucopyranosyl-DMJ (23) from A. myriophylla were isolated as new compounds.     

Variation in antibacterial and anti-inflammatory activity of different growth forms of Malva parviflora and evidence for synergism of the anti-inflammatory compounds

Malva parviflora leaves and roots were collected from five sites within the Qacha's Nek District in Lesotho. These plants had two distinct growth forms--upright and prostrate. Hexane, methanol and water extracts were made from the plant material and tested for antibacterial and anti-inflammatory activity using the disc diffusion and cyclooxygenase-1 (Cox-1) bioassays, respectively. Hexane, methanol and water extracts made from Malva parviflora with a prostrate growth form inhibited the growth of Gram-positive and Gram-negative bacteria, while extracts made from plants with an upright growth form inhibited the growth of Gram-positive bacteria only. Cox-1 anti-inflammatory activity of hexane, methanol and water extracts did not show any variation between the two growth forms. The hexane extracts of both the leaves and roots were the most inhibitory. The water extracts had the least inhibitory activity. Bioassay-guided fractionation of the root dichloromethane extract showed that Cox-1 anti-inflammatory activity was caused by at least two compounds that acted synergistically to produce the biological effect.     

Manadosterols A and B, Sulfonated Sterol Dimers Inhibiting the Ubc13-Uev1A Interaction, Isolated from the Marine Sponge Lissodendryx fibrosa

Two new dimeric sterols, manadosterols A (1) and B (2), were isolated from the marine sponge Lissodendryx fibrosa collected in Indonesia. The two compounds are comprised of two sulfonated sterol cores connected through the respective side chains. Manadosterols A (1) and B (2) inhibited the Ubc13-Uev1A interaction with IC(50) values of 0.09 and 0.13 μM, respectively. They are the second and third natural compounds showing inhibitory activities against the Ubc13-Uev1A interaction and are more potent than leucettamol A (IC(50), 106 μM), the first such inhibitor, isolated from another marine sponge.     

New butenolides from two marine streptomycetes

Chemical examination of two marine Streptomycetes has resulted in the isolation of four new butenolides, namely 4, 10-dihydroxy-10-methyl-dodec-2-en-1,4-olide (1), two diastereomeric 4,11-dihydroxy-10-methyl-dodec-2-en-1,4-olides (2/3), and 4-hydroxy-10-methyl-11-oxo-dodec-2-en-1,4-olide (4). The structures were identified by interpretation of the 2D NMR and mass spectral data.     

Trisphaerolide A,a novel polyketide from the Dominican sponge Erylus trisphaerus

The structure of trisphaerolide A (1), a mildly cytotoxic metabolite isolated from extracts of the marine sponge Erylus trisphaerus collected in Dominica, has been elucidated by detailed analysis of spectroscopic data. Trisphaerolide A (1) has a putative polyketide biogenesis, incorporating a rare variant on the standard pathway, which involves the addition of methyl branches arising from C-2 carbons of acetate units to chain carbons that arise from C-1 of acetate units.     

Pharmacological and phytochemical screening of two Hyacinthaceae species: Scilla natalensis and Ledebouria ovatifolia

Aqueous, ethanolic, dichloromethane and n-hexane extracts of Scilla natalensis Planch. and Ledebouria ovatifolia (Bak.) Jessop bulbs (Hyacinthaceae) were screened for antibacterial, anti-inflammatory, antischistosomic, anticancer and anthelmintic activity. Poor antibacterial activity against both Gram-positive and Gram-negative bacteria was shown with S. natalensis extracts. Good antibacterial activity was shown by the ethanolic and dichloromethane extracts of L. ovatifolia against Gram-positive bacteria. In the anti-inflammatory screening, the dichloromethane and hexane extracts of S. natalensis resulted in good inhibition against both COX-1 and COX-2. Ethanolic extracts had the highest inhibitory effect against nematodes in the anthelmintic assays. Poor anti-inflammatory and anthelmintic activity was found with L. ovatifolia. Aqueous extracts of S. natalensis had good activity against Schistosoma haematobium, with a minimum inhibitory concentration of 0.4 mg ml(-1). Aqueous extracts of fresh L. ovatifolia bulb material were found to be lethal to S. haematobium at a concentration of 1.6 mg ml(-1). The phytochemical screening of S. natalensis bulbs revealed the presence of saponins and bufadienolides within the bulbs. Bulbs of L. ovatifolia contained bufadienolides.     

大黄和生首乌鞣质含量对小鼠小肠推进的影响

目的研究大黄和生首乌70%乙醇提取物中鞣质含量对小鼠在体小肠推进的影响。方法用紫外分光光法测定浸膏中鞣质含量,小鼠小肠炭末推进法测定大黄及生首乌醇提物去除鞣质前后小肠的推进率。结果大黄和生首乌醇提物对小鼠小肠炭末的推进无明显影响,但去除鞣质后则呈现明显的促进作用。结论鞣质的存在明显抑制了小鼠小肠炭末的推进率,且其含量与抑制的强度呈正相关。     

Bahamaolides A and B, antifungal polyene polyol macrolides from the marine actinomycete Streptomyces sp

Bahamaolides A and B (1 and 2), two new 36-membered macrocyclic lactones, were isolated from the culture of the marine actinomycete Streptomyces sp. derived from a sediment sample collected at North Cat Cay in the Bahamas. The planar structures of 1 and 2, bearing a hexaenone and nine consecutive skipped hydroxy groups, were determined by 1D and 2D NMR, mass, IR, and UV spectra. The absolute configurations of the bahamaolides were established by combined multistep chemical reactions and spectroscopic analysis. Bahamaolide A displayed significant inhibitory activity against Candida albicans isocitrate lyase and antifungal activity against various pathogenic fungi.     

Relaxant effect of Pimpinella anisum on isolated guinea pig tracheal chains and its possible mechanism(s)

We have studied the relaxant effect of Pimpinella anisum on isolated guinea pig tracheal chains and its possible mechanism(s). The bronchodilatory effects of aqueous and ethanol extracts and essential oil were examined on precontracted isolated tracheal chains of the guinea pig by 10 microM methacholine in two different conditions including: non-incubated tissues (group 1) and incubated tissues with 1 microM propranolol and 1 microM chlorpheniramine (group 2). In addition, the anticholinergic effects of essential oil and 10 nM atropine were tested by comparing the cumulative log concentration-response curves of methacholine induced contraction of tracheal chains and the effective concentration of methacholine, causing 50% of maximum response (EC(50)) in the presence of essential oil or atropine. Aqueous and ethanol extracts, essential oil and theophylline (1 mM) showed significant relaxant effects compared to those of controls. Although relaxant effect of essential oil was lower than theophylline, there was no significant difference between the effect of aqueous and ethanol extracts and that of theophylline. There was also no significant difference between the relaxant effects obtained in group 1 and 2 experiments. The results also showed parallel rightward shifts of methacholine-response curves and significant increase in EC(50) with the presence of atropine or essential oil. These results indicated bronchodilatory effects of essential oil, aqueous, and ethanol extracts from P. anisum. The results also showed that the relaxant effect of this plant is not due to an inhibitory effect of histamine (H(1)) or stimulatory effect of beta(2)-adrenergic receptors, but due to inhibitory effects on muscarinic receptors.     

Mitochondrial respiration inhibitors suppress protein translation and hypoxic signaling via the hyperphosphorylation and inactivation of translation initiation factor eIF2α and elongation factor eEF2

Over 20,000 lipid extracts of plants and marine organisms were evaluated in a human breast tumor T47D cell-based reporter assay for hypoxia-inducible factor-1 (HIF-1) inhibitory activity. Bioassay-guided isolation and dereplication-based structure elucidation of an active extract from the Bael tree (Aegle marmelos) afforded two protolimonoids, skimmiarepin A (1) and skimmiarepin C (2). In T47D cells, 1 and 2 inhibited hypoxia-induced HIF-1 activation with IC50 values of 0.063 and 0.068 μM, respectively. Compounds 1 and 2 also suppressed hypoxic induction of the HIF-1 target genes GLUT-1 and VEGF. Mechanistic studies revealed that 1 and 2 inhibited HIF-1 activation by blocking the hypoxia-induced accumulation of HIF-1α protein. At the range of concentrations that inhibited HIF-1 activation, 1 and 2 suppressed cellular respiration by selectively inhibiting the mitochondrial electron transport chain at complex I (NADH dehydrogenase). Further investigation indicated that mitochondrial respiration inhibitors such as 1 and rotenone induced the rapid hyperphosphorylation and inhibition of translation initiation factor eIF2α and elongation factor eEF2. The inhibition of protein translation may account for the short-term exposure effects exerted by mitochondrial inhibitors on cellular signaling, while the suppression of cellular ATP production may contribute to the inhibitory effects following extended treatment periods.     

Bioactive constituents from the marine crinoid Himerometra magnipinna

A new tetrabromospirocyclohexadienylisoxazole, (+)-12-hydroxyhomoaerothionin (1), together with the known compounds (+)-aerothionin (2) and crinemodin-rhodoptilometrin bianthrone (3), were isolated from the marine crinoid Himerometra magnipinna, which had been collected in the South China Sea, Malaysia. The structure of 1 was elucidated by interpretation of 1D 1H and 13C NMR spectra and 2D 1H-1H COSY, HMQC, and HMBC spectra. This is the first report of tetrabromospirocyclohexadienylisoxazole compounds from a crinoid of Himerometra. Compounds 1-3 were evaluated for their inhibitory activity with the hyphae formation inhibition assay in Streptomyces 85E.     

Immunomodulatory response of Cramoll 1,4 lectin on experimental lymphocytes

Cramoll 1,4 is a lectin extracted from Cratylia mollis Mart. seeds that has shown antitumor and lymphocyte mitogenic activities in other studies. The aim of this work was to investigate, in vitro, the immunomodulatory activity of Cramoll 1,4 on experimental cultures of mice lymphocytes through cytotoxic assays, nitric oxide (NO) concentrations and IL-10 and IFN-γ production. Cramoll 1,4 did not show cytotoxic activity at 1-25 μg/mL concentrations, similar results were observed with concanavalin A (Con A) and phytohemagglutinin (PHA) lectins. The minimum production of IL-10 was observed in splenocytes cultivated with Con A, PHA and Cramoll 1,4 lectins. However, splenocytes treated with Cramoll 1,4 showed higher IFN-γ production in comparison with PHA and Con A (p < 0.05 for both). Production of NO was effectively suppressed in murine cells stimulated with the lectins and was only detected after 72 h for PHA in relation to non-stimulated lymphocytes (p < 0.05). Cramoll 1,4 was not toxic to murine lymphocytes, induced Th1 response through IFN-γ production and showed antiinflammatory activity through NO suppression. Therefore, Cramoll 1,4 can be considered a lectin with immunomodulatory activity.     

具有乙酰胆碱酯酶抑制活性的总生物碱提取物的筛选

目的:从采自甘肃文县和舟曲的22种植物的总生物碱提取物中筛选具有乙酰胆碱酯酶抑制活性的提取物,为进一步寻找天然乙酰胆碱酯酶抑制剂单体成分奠定基础。方法:采用酸提碱沉法提取生物碱,用改良的Ellman比色法测定总生物碱的抗乙酰胆碱酯酶活性。结果:弯柱唐松草(Thalictrumuncinulatum Franch.)、阔叶十大功劳(Mahnia bealei(Fort.)Steam.)、蚬壳花椒(Zanthoxylum dissitumHemsl.)、刺柄南星(Arisaema aspeiatum N.E.Brown)、一把伞南星(Arisaema erunescens(Wall.)Schott)、猫儿屎(Decaisnea insignis(Griff)Hook.f.et thoms)、虎耳草(Saxifraga stolonifera curt.)和西固凤仙花(Impot-iens notolopha Maxim.)的总生物碱提取物具有明显的乙酰胆碱酯酶抑制活性,其IC50值分别为2.3μg.mL-1、2.9μg.mL-1、3.5μg.mL-1、11.0μg.mL-1、16.9μg.mL-1、22.7μg....     

Boneratamides A-C, new sesquiterpenoids isolated from the marine sponge Axinyssa aplysinoides

Three new sesquiterpenoids, boneratamides A (1)-C (3), have been isolated as their methyl esters 4-6 from extracts of the marine sponge Axinyssa aplysinoides collected in Indonesia. The structures of methyl esters 4-6 were elucidated by analysis of spectroscopic data and confirmed by single-crystal X-ray diffraction analysis of 4.     

苏木不同提取物对两种口腔致龋菌的影响

目的观察苏木不同提取物对常见口腔致龋菌的影响。方法测定苏木不同提取物对粘性放线菌和变形链球菌的MIC、MBC值,观察苏木不同提取物对这两种菌的抑制产酸和抑制黏附的效果。结果苏木4种提取物对粘性放线菌和变形链球菌最低抑菌浓度(MIC)为1.25~2.50 g/L,最低杀菌浓度(MBC)均为5 g/L。1/2 MIC乙醇提取物对粘性放线菌的抑制产酸的效果最好,1/2 MIC水提取物对变形链球菌的抑制产酸效果最好,这两组效果与阳性对照组相比没有统计学差异。实验组中抑制黏附效果最好的是1/2 MIC乙醇提取物,1/2 MIC乙醇提取物对粘性放线菌和变形链球菌抑制黏附率分别为41.83%和46.40%。结论苏木4种提取物对粘性放线菌和变形链球菌都有很好的抑菌杀菌效果。其中1/2 MIC乙醇提物对粘性放线菌有好的抑制产酸效果,1/2 MIC水提取物对变形链球菌抑制产酸效果好,苏木不同提取物对粘性放线菌和变形链球菌都有抑制黏附的效果。     

Glycosidase-inhibiting pyrrolidines and pyrrolizidines with a long side chain in Scilla peruviana

2,5-Dideoxy-2,5-imino-d-glycero-d-manno-heptitol (homoDMDP) is widely distributed in Hyacinthaceae plants and can also be regarded as the alpha-1-C-(1,2-dihydroxyethyl) derivative of 1,4-dideoxy-1,4-imino-d-arabinitol (d-AB1). In a search for glycosidase inhibitors in this family of plants, we isolated three new d-AB1 derivatives bearing the 2-hydroxypropyl (1), 1,2-dihydroxypropyl (2), and 1,5,7,12,13-pentahydroxytridecyl (3) side chains at the C-1alpha position, respectively, from the bulbs of Scilla peruviana. Alkaloid 3 was a powerful inhibitor of bacterial beta-glucosidase (IC(50) = 80 nM) and bovine liver beta-galactosidase (IC(50) = 90 nM). This plant coproduced four new pyrrolizidine alkaloids, alpha-5-C-(3-hydroxybutyl)-7-epi-australine (4), alpha-5-C-(3-hydroxybutyl)hyacinthacine A(1) (5), alpha-5-C-(1,3-dihydroxybutyl)hyacinthacine A(1) (6), and alpha-5-C-(1,3,4-trihydroxybutyl)hyacinthacine A(1) (7). Alkaloids 4 and 6 were potent inhibitors of yeast alpha-glucosidase, with IC(50) values of 6.6 and 6.3 microM, respectively, and alkaloid 6 was also a potent inhibitor of bacterial beta-glucosidase with an IC(50) value of 5.1 microM.     

Apakaochtodenes A and B: two tetrahalogenated monoterpenes from the red marine alga Portieria hornemannii.

The structure of apakaochtodene A, the minor isomer of two tetrahalogenated ochtodene monoterpenes, isolated from the red marine alga Portieria hornemannii (Lyngbye) Silva has been identified as 6(S)-bromo-1,4(S),8(R)-trichloro-2(Z)-ochtodene (1) by NMR spectral and X-ray crystallographic analysis. Its geometrical isomer, apakaochtodene B (2), which could not be separated from 1 and thus characterized as a 95:5 mixture of 2:1 had (1)H and (13)C NMR spectral characteristics similar to previously known ochtodene (3) and the related tetrahalogenated monoterpene 4.