- A TRITERPENOID SAPONIN FROM FICARIA RANUNCULOIDES TUBERS
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One of the minor saponins extracted from the tubers of Ficaria ranunculoides and purified by fermentation may be 3-O-(α-arabinopyranosyl-1')28-O-6''(α-rhamnopyranosyl-1'''->4'')β-glucopyranosyl-1''>-hederagenin.On the basis of chemical degradation and spectral analysis, the structure of this new saponin is proposed. Key Word Index - Ficaria ranunculoides; Ranunculaceae; triterpenoid saponin; 3-O-(α-arabinopyranosyl-1')28-O-6''(α-rhamnopyranosyl-1'''->4'')β-glucopyranosyl 1''>-hederagenin.
- Texier, O.,Ahond, A.,Regerat, F.,Pourrat, H.
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- Cytotoxic and immunomodulator potential of hederagenin saponins from Cephalaria tchihatchewii
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Two newly described oleanane-type saponins (1–2), named tchihatchewosides A–B, along with thirteen known compounds, were isolated from the aerial parts of Cephalaria tchihatchewii using several type of chromatography processes. The structures of all compounds (1-15) were determined by spectroscopic (1D- and 2D-NMR, HR-ESI/MS) and chemical methods. The cytotoxic activities on CCD 34Lu, A549, CRL5807, CRL 5826, HTB-177 and HeLa cell lines of newly described compounds 1–2 and 1a-2a were evaluated by MTT method using doxorubicin as positive control. Immunomodulatory activity was performed with PMA plus ionomycin in stimulated whole blood cells treated with saponins. The supernatant was analyzed for IL-4, IFN-γ and IL1β cytokines by ELISA. DMSO was considered as the negative control. The results showed that the only compound 1a was exhibited moderate cytotoxicity against CRL 5826 and CCD 34Lu cells. The compounds 1–2 and prosapogenins 1a-2a stimulated IL1β cytokine release, indicating that they might potentially stimulate the innate immune response.
- Sarikahya, Nazli Boke,Mkouboi, Mohamed Chanfiou,Nalbantsoy, Ayse,Elibol, Murat
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- Antibacterial activity of a triterpenoid saponin from the stems of Caesalpinia pulcherrima Linn.
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A new compound 1 was isolated from the methanolic extract of the stems of the Caesalpinia pulcherrima Linn. along with a reported compound (2) 3-O-β-D-glucopyranosyl-(1→4)-β-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl hederagenin 28-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl ester. The new compound 1 has m.p. 272–274°C, m.f. C46H74O17, [M]+ m/z 898. It was characterised as 3-O-β-D-glucopyranosyl-(1→4)-α-L-arabinopyranosyl hederagenin 28-O-β-D- xylopyranosyl ester by various colour reactions, chemical degradations and spectral analyses. Antibacterial activity of compound 1 was screened against various Gram-positive and Gram-negative bacteria and showed significant results.
- Asati, Nidhi,Yadava
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p. 499 - 507
(2017/09/30)
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- Impact of Scaffold Exploration on Novel Dual-Acting Histone Deacetylases and Phosphodiesterase 5 Inhibitors for the Treatment of Alzheimer’s Disease
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A novel systems therapeutics approach, involving simultaneous inhibition of phosphodiesterase 5 (PDE5) and histone deacetylase (HDAC), has been validated as a potentially novel therapeutic strategy for the treatment of Alzheimer’s disease (AD). First-in-class dual inhibitors bearing a sildenafil core have been very recently reported, and the lead molecule 7 has proven this strategy in AD animal models. Because scaffolds may play a critical role in primary activities and ADME-Tox profiling as well as on intellectual property, we have explored alternative scaffolds (vardenafil- and tadalafil-based cores) and evaluated their impact on critical parameters such as primary activities, permeability, toxicity, and in vivo (pharmacokinetics and functional response in hippocampus) to identify a potential alternative lead molecule bearing a different chemotype for in vivo testing.
- Sánchez-Arias, Juan A.,Rabal, Obdulia,Cuadrado-Tejedor, Mar,De Miguel, Irene,Pérez-González, Marta,Ugarte, Ana,Sáez, Elena,Espelosin, Maria,Ursua, Susana,Haizhong, Tan,Wei, Wu,Musheng, Xu,Garcia-Osta, Ana,Oyarzabal, Julen
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p. 638 - 661
(2017/03/20)
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- Bioactive oleanane-type saponins from the rhizomes of Anemone taipaiensis
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Investigation of the n-BuOH extract of the rhizomes of Anemone taipaiensis led to the isolation of five new oleanane-type triterpenoid saponins (1-5), together with seven known saponins (6-12). Their structures were determined by the extensive use of 1D and 2D NMR experiments along with ESIMS analyses and acid hydrolysis. The aglycone of 1, 2 and 4 was determined as siaresinolic acid, which was reported in this genus for the first time. The cytotoxicities of the saponins 1-12, prosapogenins 4a, 5a, 10a-12a and sapogenins siaresinolic acid (SA), oleanolic acid (OA), hederagenin (HE) were evaluated against five human cancer cell lines, including HepG2, HL-60, A549, HeLa and U87MG. The monodesmosidic saponins 6-8, 5a, 10a-12a and sapogenins SA, OA, HE exhibited cytotoxic activity toward all cancer cell lines, with IC 50 values ranging from 2.25 to 57.28 μM. Remarkably, the bisdesmosidic saponins 1-4 and 9 showed selective cytotoxicity against the U87MG cells.
- Wang, Xiao-Yang,Gao, Hui,Zhang, Wei,Li, Yuan,Cheng, Guang,Sun, Xiao-Li,Tang, Hai-Feng
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p. 5714 - 5720
(2013/10/01)
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- Drug to genome to drug: Discovery of new antiplasmodial compounds
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Figure Presented. The dominant strategy for discovery of new antimalarial drugs relies on cell-free assays on specific biochemical pathways of Plasmodium falciparum. However, it appears that screening directly on the parasite is a more rewarding approach. The drug to genome to drug approach consists of testing a small set of structural analogues of a drug acting on human proteins that have plasmodial orthologues. Both man and plasmodium possess cyclic nucleotide phosphodiesterases (PDEs) that are key players of cell homeostasis. We synthesized and tested 40 analogues of tadalafil, a human PDE5 inhibitor, on P. falciparum in culture and obtained potent inhibitors of parasite growth. We discuss the structure-activity relationships, which support the hypothesis that our compounds kill the parasite via inhibition of plasmodial PDE activity. We also prove that antiplasmodial derivatives inhibit the hydrolysis of cyclic nucleotides of the parasite, validating the cAMP/cGMP pathways as therapeutic targets against Plasmodium falciparum.
- Beghyn, Terence B.,Charton, Julie,Leroux, Florence,Laconde, Guillaume,Bourin, Arnaud,Cos, Paul,Maes, Louis,Deprez, Benoit
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p. 3222 - 3240
(2011/06/27)
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- Triterpene glycosides from the underground parts of caulophyllum thalictroides
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A total of 22 triterpene glycosides, including 10 new compounds (1-10), were isolated from the underground parts of Caulophyllum thalictroides. The structures of the new glycosides were determined on the basis of extensive spectroscopic analyses, including two-dimensional (2D) NMR data, and of hydrolytic cleavage followed by chromatographic or spectroscopic analyses. All 22 compounds were evaluated for cytotoxicity against HL-60 human leukemia cells. The triterpene monodesmosides based on oleanolic acid (1 and 11-16) showed cytotoxic activity against HL-60 cells with IC50 values that ranged from 3.4 to 15.9 μg/mL.
- Matsuo, Yukiko,Watanabe, Kazuki,Mimaki, Yoshihiro
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experimental part
p. 1155 - 1160
(2011/03/21)
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- PDE5 inhibitors: An original access to novel potent arylated analogues of tadalafil
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A method to access totally new analogues of tadalafil was explored. The Buchwald reaction was adapted and used to replace the methyl group of tadalafil by various aryl groups. Inhibition potencies on PDE5 of these analogues were determined and proved to be comparable to the one of tadalafil. Using the same route, compounds with the same level of activity but improved water solubility were produced by introducing a pyridine or a pyrimidine ring. This original route also opens access to new unpatented compounds.
- Beghyn, Terence,Hounsou, Candide,Deprez, Benoit P.
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p. 789 - 792
(2007/10/03)
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- Triterpene glycosides from Kalopanax septemlobum. 1. Glycosides A, B, C, F, G1, G2, I2, H, and J from leaves of Kalopanax septemlobum var. maximowichii introduced to Crimea
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Eight known glycosides of hederagenin and the new triterpene glycoside 3-O-β-D-xylopyranosyl-(1→3)-O-α-L-rhamnopyranosyl-(1→2) -O-α-L-arabinopyranosyl-28-O-α-L-rhamnopyranosyl-(1→4) -O-6-O-acetyl-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranosyl ester of hederagenin were isolated by chromatographic methods from leaves of Kalopanax septemlobum var. maximowichii introduced to Crimea. The known 3-O-α-L-arabinopyranosyl-28-O-α-L-rhamnopyranosyl-(1→4) -O-6-O-acetyl-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranosyl ester of hederagenin was observed for the first time in Kalopanax septemlobum. 2005 Springer Science + Business Media, Inc.
- Grishkovets,Panov,Kachala,Shashkov
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p. 194 - 199
(2008/02/01)
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- The discovery of tadalafil: A novel and highly selective PDE5 inhibitor. 2: 2,3,6,7,12,12a-Hexahydropyrazino[1′,2′ :1,6]pyrido[3,4-b]indole-1,4-dione analogues
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Modification of the hydantoin ring in the previously described lead compound 2a has led to the discovery of compound 12a, tadalafil, a highly potent and highly selective PDE5 inhibitor. The replacement of the hydantoin in compound 2a by a piperazinedione ring led to compound cis-11a which showed similar PDE5 inhibitory potency. Introduction of a 3,4-methylenedioxy substitution on the phenyl ring in position 6 led to a potent PDE5 inhibitor cis-11c with increased cellular potency. Optimization of the chain on the piperazinedione ring led to the identification of the racemic cis-N-methyl derivative 11i. High diastereospecificity for PDE5 inhibition was observed in the piperazinedione series with the cis-(6R,12aR) enantiomer displaying the highest PDE5 inhibitory activity. The piperazinedione 12a, tadalafil (GF196960), has been identified as a highly potent PDE5 inhibitor (IC50 = 5 nM) with high selectivity for PDE5 vs PDE1-4 and PDE6. Compound 12a displays 85-fold greater selectivity vs PDE6 than sildenafil 1. 12a showed profound and long-lasting blood pressure lowering activity (30 mmHg/>7 h) in the spontaneously hypertensive rat model after oral administration (5 mg/kg).
- Daugan, Alain,Grondin, Pascal,Ruault, Cécile,Le Monnier de Gouville, Anne-Charlotte,Coste, Hervé,Linget, Jean Michel,Kirilovsky, Jorge,Hyafil, Fran?ois,Labaudinièret, Richard
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p. 4533 - 4542
(2007/10/03)
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- Two new antifungal saponins from the Tibetan herbal medicine Clematis tangutica
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Bioassay-guided fractionation of the ethanol extract of the aerial parts of Clematis tangutica led to the isolation of two new antifungal triterpene saponins. Their structures were determined to be 3-O-α-L-arabinopyranosyl hederagenin 28-O-α-L-rhamnopyranosyl ester (1) and 3-O-β-D-glucopyranosyl-(1→4)-α-L-arabinopyranosyl hederagenin 28-O-α-L-rhamnopyranosyl ester (2) on the basis of spectral data and chemical evidence. Inhibitory activities of the two saponins against seven fungal strains were evaluated. Compounds 1 and 2 showed evident antifungal activity (MIA ≈ 2.5 μg/disc) against Saccharomyces cerevisiae, similar to the positive control amphotericin B and ordinary activities (MIA ≈ 10 μg/disc) against Penicillium avellaneum UC-4376, Candida glabrata, Trichosporon beigelii and Pyricularia oryzae. Compound 2 is a better antifungal agent than compound 1 against most of the fungal strains that were tested.
- Du, Zhizhi,Zhu, Na,Ze-Ren-Wang-Mu, Na,Shen, Yuemao
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p. 547 - 551
(2007/10/03)
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- Method of treating nitrate-induced tolerance
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The present invention relates to methods for treating nitrate-induced tolerance in a mammal by administering a nitrate-induced tolerance treating amount of a compound of formulae (I), (II), (III) (IV), (V), (VI), (VII), (VIII), (IX), (XA) or (XB) as defined herein, or the pharmaceutically acceptable salts, prodrugs, polymorphs, hydrates, solvates, active metabolites or stereoisomers thereof. The invention also relates to pharmaceutical compositions for the treatment of nitrate-induced tolerance in a mammal comprising a nitrate-induced tolerance treating amount of a compound of formulae (I), (II), (III) (IV), (V), (VI), (VII), (VIII), (IX), (XA) or (XB) as defined herein, or the pharmaceutically acceptable salts, prodrugs, polymorphs, hydrates, solvates, active metabolites or stereoisomers thereof, and a pharmaceutically acceptable vehicle, diluent or carrier. The invention further relates to methods of preventing nitrate-induced tolerance in a mammal comprising administering a nitrate-induced tolerance preventing amount of a cGMP PDE inhibitor.
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- Triterpenoid glycosides of Fatsia japonica. II. Isolation and structure of glycosides from the leaves
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The previously known triterpenoid 3-O-α-L-arabinopyranosides of oleanolic and echinocystic acids and hederagenin, 3-O-β-D-glucopyranosyl-(1→2)-O-α-L-arabinopyranosides of oleanolic acid and hederagenin, in addition to 28-O-α-L-rhamnopyranosyl-(1→4)-O-β-D-glucopyranosyl-(1→6)-O-β-D-glucopyranosyl ethers of the 3-O-α-L-arabinopyranoside of hederagenin, and 3-O-β-D-glucopyranosyl-(1→2)-O-α-L-arabinopyranosides of oleanolic acid and hederagenin, respectively, are isolated from leaves of Fatsia japonica (Araliaceae). The structures of the glycosides are confirmed by chemical methods and 13C NMR spectroscopy.
- Grishkovets,Sobolev,Shashkov,Chirva
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p. 501 - 505
(2007/10/03)
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- Metabolism of kalopanaxsaponin B and H by human intestinal bacteria and antidiabetic activity of their metabolites
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To investigate the relationship between the intestinal bacterial metabolism of kalopanaxsaponin B and H from Kalopanax pictus (Araliaceae), and their antidiabetic effect, kalopanaxsaponin B and H were metabolized by human intestinal microflora and the antidiabetic activity of their metabolites was measured. Human intestinal microflora metabolized kalopanaxsaponin B to kalopanaxsaponin A, hederagenin 3-O-α-L- arabinopyranoside and hederagenin. The main metabolites of kalopanaxsaponin B were kalopanaxsaponin A and hederagenin. Kalopanaxsaponin H was metabolized to kalopanaxsaponin A and I, hederagenin 3-O-α-L-arabinopyranoside and hederagenin. The main metabolites of kalopanaxsaponin H were kalopanaxsaponin I and hederagenin. Among kalopanaxsaponin B, H and their metabolites, kalopanaxsaponin A showed the most potent antidiabetic activity, followed by hederagenin. However, the main components, kalopanaxsaponin B and H, in K. pictus were inactive.
- Kim, Dong-Hyun,Yu, Ki-Woong,Bae, Eun-Ah,Park, Hee-Juhn,Choi, Jong-Won
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p. 360 - 365
(2007/10/03)
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- Thermal Degradation of Glycosides, V - Hydrothermolysis of Triterpenoid and Steroid Glycosides
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In this paper the hydrothermolysis of triterpenoid and steroid glycosides is described.By mere heating with water or water/1,4-dioxane solution, the triterpenoid and steroid glycosides 1, 4 and 15, 16, 25, 29, respectively, are converted into their aglycones and prosapogenins.Furthermore, hydrothermolysis of the triterpenoid 3,28-O-bisglycosides 5, 6, 8, 9, 12 affords the corresponding 3-O-glycosides and reduced oligosaccharides formed by selective cleavage of the ester glycosidic linkage.It is expected that this hydrothermolysis is useful for the structure determination of some triterpenoid and steroid glycosides and for yielding new oligosaccharides.The hydrothermolyzed products have been isolated by chromatography and their structures elucidated by spectroscopic methods.Key Words: Degradation, thermal / Thermolysis / Glycosides / Carbohydrates / Triterpenoids / Steroids
- Kim, Youn Chul,Higuchi, Ryuichi,Komori, Tetsuya
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p. 453 - 460
(2007/10/02)
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- Degradation of Cardenolide Glycosides
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The thermal degradation of cardenolide glycosides consisting of different sugar moieties and aglycones was examined.On simple heating, the sugar - aglycone linkage of cardenolide glycosides having 2,6-dideoxy sugar moieties is readily cleaved, to afford their genuine aglycones.On the contrary, cardenolide glycosides possessing 6-deoxy sugar moieties are resistant to the degradative reaction.Besides the fission of the glycosidic linkages, some interesting reactions also took place.The pyrolyzed products were isolated by chromatography, and the structures were elucidated by spectroscopic evidence.
- Kim, Youn Chul,Higuchi, Ryuichi,Komori, Tetsuya,Abe, Fumiko,Yamauchi, Tatsuo
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p. 943 - 947
(2007/10/02)
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- TRITERPENE SAPONINS OF Caltha polypetala. GLYCOSIDES G and I
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From the epigeal organs of the great march marigold (family Ranunculaceae) two triterpene glycosides, a tetra- and a pentaoside of hederagenin, have been isolated.Their chemical structures have been established by chemical methods of investigation and by 1H and 13C NMR spectroscopy.Glycoside G is hederagenin 3-O-α-L-arabinoside 28-O- 4)-O-β-D-glucopyranosyl-(1 -> 6)-β-D-glucopyranoside>.Glycoside I is hederagenin 3-O- 2)-α-L-arabinoside 28-O- 4)-O-β-D-glucopyranosyl-(1 -> 6)-β-D-glucopyranoside>.
- Vugalter, M. M.,Dekanosidze, G. E.,Dzhikiya, O. D.,Shashkov, A. S.,Kemertelidze, E. P.
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p. 193 - 200
(2007/10/02)
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- Studies on the constituents of Hedera rhombea Bean. IV. On the hederagenin glycosides
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On the basis of chemical and physicochemical evidence, the structures of two new hederagenin bisdesmosides, named Kizuta saponins K8 (X) and K11 (I), which were isolated from the stem and bark of Hedera rhombea Bean (Araliaceae), were established to be as follows: X, 3-O-α-L-arabinopyranosyl-hederagenin 28-O-α-L-rhamnopyranosyl-(1 →4)-6-O-acetyl-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl ester; I,3-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl-hederagenin 28-O-α-L-rhamnopyranosyl(1→4)-6-O-acetyl-β-D-glucopyranosyl-(1→6)-β-D -glucopyranosyl ester. A glucoside mixture (XIII) was considered to be a mixture of the β-D glucopyranosides of campesterol (trace), stigmasterol and β-sitosterol based on chemical and physicochemical evidence.
- Kizu,Hirabayashi,Suzuki,Tomimori
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p. 3473 - 3478
(2007/10/02)
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- STRUCTURES OF 3,28-O-BISGLYCOSIDIC TRITERPENOID SAPONINS OF FATSIA JAPONICA
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Four novel 3,28-O-bisglycosidic triterpenoid saponins were isolated from the mature fruits of F. japonica.They were characterized as the 28-O-α-L-rhamnopyranosyl-(1->4)-β-D-glucopyranosyl-(1->4)-β-D-glucopyranosides of 3-O-α-L-arabinopyranosyl echinocystic acid, 3-O-α-L-arabinopyranosyl hederagenin, 3-O-β-D-glucopyranosyl-(1->2)-α-L-arabinopyranosyl oleanolic acid and 3-O-β-D-glucopyranosyl-(1->2)-α-L-arabinopyranosyl hederagenin respectively. - Keywords: Fatsia japonica; Araliaceae; mature fruits; 3,28-O-bisglycidic triterpenoid saponins.
- Akoi, Tadashi,Shido, Kazumi,Takahashi, Yutaka,Suga, Takayuki
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p. 1681 - 1686
(2007/10/02)
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