共查询到20条相似文献,搜索用时 31 毫秒
1.
Tsutomu Masuda Kunio Yamane Hideo Hirokawa Teruo Tanaka Kenji Sakaguchi Bunji Maruo 《Bioscience, biotechnology, and biochemistry》2013,77(4):947-948
Five bufadienolides (1-5) isolated from the leaves of Kalanchoe pinnata and K. daigremontiana×tubiflora (Crassulaceae) were examined for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation in Raji cells induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate. All bufadienolides showed inhibitory activity, and bryophyllin A (1) exhibited the most marked inhibition (IC50=0.4 μM) among the tested compounds. Bryophyllin C (2), a reduction analogue of 1, and bersaldegenin-3-acetate (3) lacking the orthoacetate moiety were less active. These results strongly suggest that bufadienolides are potential cancer chemopreventive agents. 相似文献
2.
Satoshi Numazawa Masa-Aki Shinoki Hisatomi Ito Takemi Yoshida Yukio Kuroiwa 《Journal of cellular physiology》1994,160(1):113-120
Human leukemia K562 cell differentiation induction by naturally occurring bufadienolides purified from the Chinese drug Senso and synthetic bufalin derivatives was examined by a nitro blue tetrazolium reduction assay. Bufalin showed the strongest activity among all the bufadienolides tested in this study. The degree of the induction of nitro blue diformazan positive cells by the bufadienolides correlated well with their inhibitory activities against Na+, K+ -ATPase prepared from K562 cells in vitro. N+, K+ -ATPases from a variant K562 clone (ouabain resistant, OuaR) and murine leukemia cell line M1-T22, which were insensitive to the bufadienolides in terms of growth inhibition and cell differentiation, appeared to be refractory to bufalin in vitro. A binding study of 3H-bufalin and 3H-ouabain revealed that saturated levels of both ligands associated with K562 cells were virtually similar; however, affinity of 3H-bufalin was considerably higher than 3H-ouabain. The saturated level of 3H-bufalin observed in the OuaR cells was approximately half of that observed in K562 cells without a change in its affinity. Association of 3H-bufalin with K562 cells was completely blocked by pretreatment of the cells with cold ouabain at concentrations saturating the binding sites. These results suggest that bufalin acts on the cells by binding to sites on the cell membrane which also bind ouabain. It is thus proposed that N+, K+ -ATPase inhibition is closely related to the initiation process in the induction of K562 cell differentiation induced by bufalin. © 1994 Wiley-Liss, Inc. 相似文献
3.
Matsuda H Kageura T Toguchida I Murakami T Kishi A Yoshikawa M 《Bioorganic & medicinal chemistry letters》1999,9(21):3081-3086
The methanolic extract from a Chinese herbal medicine, the rhizome of Alisma orientale, was found to exhibit inhibitory activity of nitric oxide (NO) production in lipopolysaccharide (LPS)activated macrophages. Novel triterpenes, alismaketones-B 23-acetate and -C 23-acetate, were isolated from the active extract together with eight sesquiterpenes and eighteen protostane-type triterpenes. The absolute stereostructures of new triterpenes were characterized on the basis of chemical and physicochemical evidence, which included the chemical correlations with known triterpenes. The guaiane-type sesquiterpenes (alismol, orientalols A and C) and protostane- and seco-protostane-types triterpenes (alisols C monoacetate, E-23-acetate, F, H, I, L-23-acetate, and M-23-acetate, alismaketones-B 23-acetate and -C 23-acetate, alismalactone 23-acetate, and 3-methylalismalactone 23-acetate) inhibited LPS-induced NO production (IC50 = 8.4-68 microM). Other triterpenes (alisols A, A monoacetate, B, B monoacetate, E, G, K-23-acetate, and N-23-acetate and 11-deoxyalisol B) also showed the potent inhibitory activity, but they showed cytotoxic effects more than 30 microM (MTT assay). In addition, alismol and alisol F were found to suppress iNOS induction. 相似文献
4.
Ye M Guo H Guo H Han J Guo D 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2006,838(2):86-95
ChanSu (toad venom) is a traditional Chinese medicine for the treatment of serious liver and gastric cancers. The major cytotoxic compounds in ChanSu are bufadienolides. In this paper, a strategy combining qualitative LC/MS analysis and quantitative HPLC determination of major bufadienolides was used for global quality control of ChanSu crude drug. Majority of the bufadienolides in methanol extract of ChanSu were unambiguously characterized by high-performance liquid chromatography coupled with atmospheric pressure chemical ionization tandem mass spectrometry (HPLC/APCI-MS/MS), and by comparing with pure compounds. In addition, eight major bufadienolides were simultaneously determined in one single HPLC run within 30 min with photodiode array detection (DAD). All compounds showed good linearity in a wide concentration range, and their limits of detection (LOD) were around 1 ng. Thus, > 95% of the bufadienolides in ChanSu could be characterized, and > 90% of them were quantitated. The established method is rapid, simple and sensitive, and could be used for the routine analysis of ChanSu crude drug and its preparations. This research sets a good example for the comprehensive quality control of traditional medicine. 相似文献
5.
The bufadienolides, 6beta-acetoxy-3beta,8beta,12beta,14beta-tetrahydroxybufa-4,20,22-trienolide (12beta-hydroxyscillirosidin) (1) and 14beta-hydroxybufa-4,20,22-trienolide 3beta-O-[alpha-L-rhamnopyranosyl-[(1-->4)-beta-D-glucopyranosyl]-(1-->3)-alpha-L-rhamnopyranoside] (urginin) (2) were isolated from Drimia robusta and Urginea altissima, respectively. 相似文献
6.
Hosoda A Nomura E Murakami A Koshimizu K Ohigashi H Mizuno K Taniguchi H 《Bioorganic & medicinal chemistry letters》2000,10(13):1439-1442
Ester compounds consisting of ferulic acid and myo-inositol, obtained from rice bran, were synthesized. The inhibitory effects of these feruloyl-myo-inositols on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced superoxide (O2-) generation were examined using differentiated HL-60 cells. Among the derivatives tested, only 3,4,5,6-tetra-O-acetyl-1,2-di-O-[3-(4'-acetoxy-3'-methoxyphenyl)-2-pr openoyl]-myo-inositol (3) showed a distinct inhibitory activity. 相似文献
7.
Anti-tumor promoting effects of sesquiterpenes from Maytenus cuzcoina (Celastraceae) 总被引:3,自引:0,他引:3
González AG Tincusi BM Bazzocchi IL Tokuda H Nishino H Konoshima T Jiménez IA Ravelo AG 《Bioorganic & medicinal chemistry》2000,8(7):1773-1778
Ten sesquiterpenoids (1-10), with a dihydro-beta-agarofuran skeleton, were isolated from Maytenus cuzcoina (Celastraceae). Their structures were elucidated on the basis of spectral analysis, including homo- and heteronuclear correlations NMR experiments (COSY, ROESY, HMQC and HMBC), and chemical correlations. The compounds have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. Compounds 1-3, 6 and 7 showed strong inhibitory effects on EBV-EA induction (100% inhibition at 1000 mol ratio/TPA). Their structure-activity relationship is discussed. 相似文献
8.
Philip J. Hilton William McKinnon Edward C. Gravett Jean-Marie R. Peron Christopher M. Frampton M. Gary Nicholls Gwyn Lord 《Steroids》2010,75(13-14):1137-1145
Partial inhibition of the sodium pump (Na/K-ATP-ase) by a circulating inhibitor is known to occur in humans. The objectives of this study were to determine the effects of novel bufadienolides lacking an oxygen at C14 on sodium pumps in human erythrocytes and leucocytes, dog kidney and pig brain and to document the importance of the stereochemistry at C17 on the ability to inhibit these sodium pumps. 14α bufadienolides were weak inhibitors of all preparations studied. 3ß-OH,5ß,14ß bufadienolide produced near-total inhibition of dog kidney and pig brain Na/K-ATP-ase. Over the same concentration range, it maximally inhibited the sodium pump of erythrocytes by 70% and leucocytes by 47%. The inhibition profile induced in the leucocyte sodium pump deviated significantly from the simple sigmoidal relationship present in the other preparations over the 3 × 10?5 to 1 × 10?7 mol/l concentration range. Allo-emicymarin (17α) was confirmed to be a weak inhibitor of the sodium pump/ATP-ase compared with emicymarin (17ß) but both were weaker inhibitors of the leucocyte sodium pump than that of the other preparations. Molecules with the C14 in the ß configuration are more efficacious than in the α configuration. In the case of emicymarin, the attachment of the furone at C17 in the α configuration results in substantially weaker inhibitory activity than in the beta configuration, seen in most cardenolides and bufadienolides. Unlike ouabain and bufalin that show no specificity of action in these preparations, 3ß- OH,5ß,14ß bufadienolide selectively inhibits the activity of at least one low-prevalence subset of the leucocyte Na/K-ATP-ase. 相似文献
9.
As a continuation to our previous work concerning antitumor benzimidazoles, we have synthesized series of new derivatives of 2-(1-benzyl-2-methyl-1H-benzimidazol-5-ylimino)-3-(substituted)-thiazolidin-4-one (6a-e), 3-(2-methyl-1H-benzimidazol-5-yl)-2-substituted-thiazolidin-4-one (9a-f) and we have studied their inhibitory activity against the Epstein-Barr virus-early antigen (EBV-EA) activation introduced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Compound 6d was found to be significantly active and compounds 5a and 6e were also active. 相似文献
10.
Yang WM Liu JK Qin XD Wu WL Chen ZH 《Zeitschrift für Naturforschung. C, Journal of biosciences》2004,59(7-8):481-484
In vitro antioxidant activities of three sweet dihydrochalcone glucosides from the leaves of Lithocarpus pachyphyllus (Kurz) Rehd. (Fagaceae), trilobatin 2"-acetate (1), phloridzin (2) and trilobatin (3), were investigated. The IC50 (50% inhibitory concentration) values for compounds 1-3 of lipid peroxidation in rat liver homogenate were 261, 28, 88 microM, respectively. Compounds 1-3 increased superoxide dismutase (SOD) activity with EC50 (50% effective concentration) values of 575, 167, 128 microM, and glutathione peroxidase (GSH-Px) activity with EC50 values of 717, 347, 129 microM, respectively, and showed only weak DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity. 相似文献
11.
Microbial transformation of three bufadienolides by Nocardia sp. and some insight for the cytotoxic structure-activity relationship (SAR) 总被引:1,自引:0,他引:1
Resibufogenin, cinobufagin, and bufalin are cytotoxic steroids isolated from the Chinese drug Chan'su. Biotransformation of these three bufadienolides by Nocardia sp. NRRL 5646 was investigated. Notably, resibufogenin was converted to 3-acetyl 15beta-hydroxyl bufotalin, via an unprecedented 14beta,15beta-epoxy ring cleavage and a regio-selective acetoxylation. This product showed significantly increased cytotoxic activity. The regio-selective acetylation of the 3-OH was also involved in the other reactions. The structures of metabolites were established by ESI-LC/MS and 2D NMR techniques. The in vitro cytotoxic activities against human cancer cell lines of the substrates and the transformed products were determined by the MTT method and their structure-activity relationship (SAR) was discussed. This investigation provided a useful approach to prepare new bufadienolides and the SAR research. 相似文献
12.
Mebs D Wagner MG Pogoda W Maneyro R Kwet A Kauert G 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2007,144(4):398-402
The South-American red bellied toads (Melanophryniscus spp.) belonging to the Bufonidae family contain toxic alkaloids in their skin, predominantly of the pumiliotoxin group. Whole animal methanolic extracts of individual specimens of three species (Melanophryniscus atroluteus, M. devincenzii, and M. montevidensis) were analyzed for the presence of toad specific bufadienolides and indolalkylamines (serotonin derivatives) by HPLC-electrospray (ESI)-MS-TOF. No bufadienolides, but few bufotenines, mainly dehydrobufotenine, were detected in the extracts in variable amounts. The concentration of the dehydrobufotenine in the extracts seems to be species specific. Whereas M. atroluteus and M. montevidensis contain very low or trace amounts, M. devincenzii specimens exhibit high concentrations of this indolalkylamine. In comparison, analysis of extracts from Bufo arenarum (Uruguay) and from B. bufo (Germany) confirmed the presence of bufadienolides as well as of bufotenine derivatives. Tadpoles of both species exhibited a different pattern: extracts from B. arenarum tadpoles contained only dehydrobufotenine, but those from B. bufo tadpoles bufotoxin and two alkylamines. Melanophryniscus toads appear not to be able to compensate the high variability of toxic skin alkaloids by producing defensive bufadienolides. 相似文献
13.
Supratman U Fujita T Akiyama K Hayashi H 《Bioscience, biotechnology, and biochemistry》2000,64(6):1310-1312
Two insecticidal bufadienolides (1 and 2) were isolated from a methanol extract of the leaves of Kalanchoe pinnata by bioassay-guided fractionation. Compound 1 was identified as known bryophyllin A (bryotoxin C). The structure of new bufadienolide 2, named bryophyllin C, was determined by spectroscopic methods and the chemical transformation of 1. Compounds 1 and 2 showed strong insecticidal activity against third instar larvae of the silkworm (Bombyx mori), their LD50 values being evaluated as 3 and 5 microg/g of diet, respectively. 相似文献
14.
Nakata T Yamada T Taji S Ohishi H Wada S Tokuda H Sakuma K Tanaka R 《Bioorganic & medicinal chemistry》2007,15(1):257-264
Two new lanostane-type triterpenoids, inonotsuoxides A (1) and B (2) along with three known lanostane-type triterpenoids, inotodiol (3), trametenolic acid (4), and lanosterol (5), were isolated from the sclerotia of Inonotus obliquus (Pers.: Fr.) (Japanese name: Kabanoanakake) (Russian name: Chaga). Their structures were determined to be 22R,25-epoxylanost-8-ene-3beta,24S-diol (1) and 22S,25-epoxylanost-8-ene-3beta,24S-diol (2) on the basis of spectral data including single crystal X-ray analysis. These compounds except for 2 were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. The most abundant triterpene, inotodiol (3), was investigated for the inhibitory effect in a two-stage carcinogenesis test on mouse skin using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. Compound 3 was found to exhibit the potent anti-tumor promoting activity in the in vivo carcinogenesis test. 相似文献
15.
Wang PC Ran XH Chen R Luo HR Ma QY Liu YQ Hu JM Huang SZ Jiang HZ Chen ZQ Zhou J Zhao YX 《化学与生物多样性》2011,8(10):1908-1913
Two new guaiane-type sesquiterpenoids, valerol A (1) and kessyl 3-acetate (2), together with nine known compounds, valeracetate (3), anismol A (4), orientalol C (5), spatulenol (6), 4α,10α-epoxyaromadendrane (7), (+)-8-hydroxypinoresinol (8), pinorespiol (9), pinoresinol 4-O-β-D-glucopyranoside (10), and 8-hydroxypinoresinol 4'-O-β-D-glucopyranoside (11) were isolated from the roots of Valeriana officinalis. The structures and relative configurations of 1 and 2 were elucidated on the basis of spectroscopic methods (1D- and 2D-NMR, MS, UV, and IR). These compounds were evaluated for inhibitory activity on acetylcholinesterase (AChE) and enhancing activity on nerve growth factor (NGF)-mediated neurite outgrowth in PC12 cells. 相似文献
16.
In a search for cancer chemopreventive agents from natural sources, four lupane-type and seven oleanane-type triterpenoids, and ten synthetic analogs were screened as potential anti-tumor promoters by using the in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) activation assay. Among them, 25-acetoxy-3alpha-hydroxyolean-12-en-28-oic acid (1) and 3beta,25-epoxy-3alpha-hydroxylup-20(29)-en-28-oic acid (2) were examined for anti-tumor promoting activity in a two-stage carcinogenesis assay on mouse skin with 7,12-dimethylbenz[a]anthracene (DMBA) and TPA as promoter. 25-Acetoxy-3alpha-hydroxyolean-12-en-28-oic acid (1) and 3beta,25-epoxy-3alpha-hydroxylup-20(29)-en-28-oic acid (2) showed moderate inhibitory activities. 相似文献
17.
Sacau EP Estévez-Braun A Ravelo AG Ferro EA Tokuda H Mukainaka T Nishino H 《Bioorganic & medicinal chemistry》2003,11(4):483-488
Sixteen derivatives (2-17) synthesized from the naphthoquinone lapachol (1), were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), as a test for potential cancer chemopreventive agents. They exhibited a variety of inhibitory activities from very high to moderate, which allow us to suggest structure-activity relationships. Ten of these derivatives are reported for the first time, their structures being thoroughly determined by spectroscopic methods. 相似文献
18.
Pei YH Kim JW Kang HB Lee HK Kim CS Song HH Chin YW Oh SR 《Bioorganic & medicinal chemistry letters》2012,22(6):2318-2320
Bioactivity-guided fractionation on the leaves of Aleurites fordii led to the isolation of a new tigliane diterpene ester, 12-O-hexadecanoyl-7-oxo-5-ene-16-hydroxyphorbol-13-acetate (1) along with four known compounds, 12-O-hexadecanoyl-7-oxo-5-ene-phorbol-13-acetate (2), 12-O-hexadecanoyl-phorbol-13-acetate (3), 12-O-hexadecanoyl-16-hydroxyphorbol-13-acetate (4), and 12-O-hexadecanoyl-4-deoxy-4α-16-hydroxyphorbol-13-acetate (5). The structures of these compounds were determined by interpretation of NMR (1D and 2D) spectroscopic data and MS data. All the isolates were evaluated for their effects on the induction of IFN-γ in NK92 cells. Compounds 3 and 4 exhibited the most potent responses in IFN-γ induction, comparable to the positive control, phorbol 12-myristate 13-acetate (PMA). 相似文献
19.
Hydroxylation is an important route to synthesize more hydrophilic compounds of pharmaceutical significance. Microbial hydroxylation offers advantages over chemical means for its high specificity. In this study, a fungal strain Alternaria alternata AS 3.4578 was found to be able to catalyze the specific 12beta-hydroxylation of a variety of cytotoxic bufadienolides. Cinobufagin and resibufogenin could be completely metabolized by A. alternata to generate their 12beta-hydroxylated products in high yields (>90%) within 8 h of incubation. A. alternata could also convert 3-epi-desacetylcinobufagin into 3-epi-12beta-hydroxyl desacetylcinobufagin as the major product (70% yield). C-3 dehydrogenated products were detected in these reactions in fair yields, while their accumulation was relatively slow. The 12beta-hydroxylation of bufadienolides could be significantly inhibited by the substitution of 1beta-, 5-, or 16alpha-hydroxyl groups, and the 14beta,15beta-epoxy ring appeared to be a necessary structural requirement for the specificity. For the biotransformation of bufalin, a 14beta-OH bufadienolide, this reaction was not specific, and accompanied by 7beta-hydroxylation as a parallel and competing metabolic route. The biotransformation products were identified by comparison with authentic samples or tentatively characterized by high-performance liquid chromatography-diode array detection-atmospheric pressure chemical ionization-mass spectrometry analyses. 相似文献
20.
Triterpene acids from the leaves of Perilla frutescens and their anti-inflammatory and antitumor-promoting effects 总被引:13,自引:0,他引:13
Banno N Akihisa T Tokuda H Yasukawa K Higashihara H Ukiya M Watanabe K Kimura Y Hasegawa J Nishino H 《Bioscience, biotechnology, and biochemistry》2004,68(1):85-90
Nine triterpene acids, viz., six of the ursane type, ursolic acid (1), corosolic acid (2), 3-epicorosolic acid (3), pomolic acid (4), tormentic acid (5) and hyptadienic acid (6), and three of the oleanane type, oleanolic acid (7), augustic acid (8) and 3-epimaslinic acid (9), among which 1 constituted the most predominant triterpene acid, were isolated and identified from ethanol extracts of the leaves of red perilla [Perilla frutescens (L.) Britton var. acuta Kudo] and green perilla [P. frutescens (L.) Britton var. acuta Kudo forma viridis Makino]. These eight compounds, 1, 2, 4-9, were evaluated for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 microg/ear) in mice. All the compounds tested showed a marked anti-inflammatory effect, with a 50% inhibitory dose (ID50) of 0.09-0.3 mg per ear. In addition, an evaluation against the Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA showed five compounds, 1-3, 5 and 9, with a potent inhibitory effect on EBV-EA induction (91-93% inhibition at 1x10(3) mol ratio/TPA). Furthermore, compound 5 exhibited strong antitumor-promoting activity in an in vivo two-stage carcinogenesis test of mouse tumor by using 7,12-dimethylbenz(a)anthracene (DMBA) as an initiator and TPA as a promoter. 相似文献