Showing papers in "Chemical & Pharmaceutical Bulletin in 1998"
TL;DR: 4,5-diaminofluorescein (DAF-2) is developed as a novel fluorescent indicator for NO that affords high sensitivity for NO and should be useful for studies of the dynamic biological actions of NO at the molecular level with fine temporal and spatial resolution.
Abstract: Endogenous nitric oxide (NO) appears to modulate many physiological and pathophysiological processes. In order to obtain direct evidence for NO functions in vivo, we have developed 4,5-diaminofluorescein (DAF-2) as a novel fluorescent indicator for NO. Green-fluorescent triazolofluorescein formed by the reaction of NO and DAF-2 affords high sensitivity for NO (detection limit: 5 nM). Membrane-permeable DAF-2 diacetate (DAF-2 DA) was loaded into activated rat aortic smooth muscle cells, where the ester bonds are hydrolyzed by intracellular esterase, generating DAF-2. The fluorescence in the cells increased in a NO concentration-dependent manner. This imaging method should be useful for studies of the dynamic biological actions of NO at the molecular level with fine temporal and spatial resolution.
279 citations
TL;DR: Two new lanostane-type triterpenes, lucidumol A and ganoderic acid beta, were isolated from the spores of Ganoderma (G.) lucidum and showed significant anti-human immunodeficiency virus (anti-HIV)-1 protease activity with IC50 values of 20-90 microM.
Abstract: Two new lanostane-type triterpenes, lucidumol A and ganoderic acid beta, were isolated from the spores of Ganoderma (G) lucidum, together with a new natural one and seven that were known The structures of the new triterpenes were determined as (24S)-24,25-dihydroxylanost-8-ene-3,7-dione and 3 beta,7 beta-dihydroxy-11,15-dioxolanosta-8,24(E)-dien-26-oic acid, respectively, by chemical and spectroscopic means The quantitative analyses of 5 fruiting bodies, antlered form and spores of G lucidum were performed by high performance liquid chromatography and demonstrated that ganoderic alcohol and acid contents were quite high in the spore Of the compound isolated, ganoderic acid beta, (24S)-lanosta-7,9(11)-diene-3 beta,24,25-triol (called lucidumol B), ganodermanondiol, ganodermanontriol and ganolucidic acid A showed significant anti-human immunodeficiency virus (anti-HIV)-1 protease activity with IC50 values of 20-90 microM
260 citations
TL;DR: A potent natural alpha-glucosidase inhibitor called kotalanol has been isolated from an antidiabetic traditional Ayurvedic medicine, the roots and stems of Salacia reticulata Wight, through bioassay-guided separation.
Abstract: A potent natural α-glucosidase inhibitor called kotalanol has been isolated from an antidiabetic traditional Ayurvedic medicine, the roots and stems of Salacia reticulata WIGHT, through bioassay-guided separation. The structure of kotalanol was elucidated on the basis of chemical and physicochemical evidence to be the inner salt comprised of 1-deoxyheptosyl-3-sulfate anion and 1-deoxy-4-thio-D-arabinofuranosyl sulfonium cation. Kotalanol was found to show more potent inhibitory activity against sucrase than salacinol and acarbose.
245 citations
TL;DR: A new sulfolipid, KM043, which belongs to the 6-sulfo-alpha-D-quinovopyranosyl-(1-->3')-1',2'-diacylglycerol (SQDG) class of compounds, has been isolated from a marine red alga as a potent inhibitor of eukaryotic DNA polymerases and HIV-reverse transcriptase type 1.
Abstract: A new sulfolipid, KM043, which belongs to the 6-sulfo-α-D-quinovopyranosyl-(1→3')-1', 2'-diacylglycerol (SQDG) class of compounds, has been isolated from a marine red alga, Gigartina tenella, as a potent inhibitor of eukaryotic DNA polymerases and HIV-reverse transcriptase type 1. Its structure was determined on the basis of spectroscopic and gas chromatographic analyses. The inhibition was dose-dependent, and complete (more than 90%)inhibition of DNA polymerase α (pol. α), DNA polymerase β (pol. β) and HIV-reverse transcriptase type 1 (HIV-RT) was observed at concentrations of 5, 10, and 30 μM, respectively.
168 citations
TL;DR: A new type of kappa-agonist, 17-cyclopropylmethyl-3, 14 beta-dihydroxy-4,5 alpha-epoxy-6 beta-[N-methyl-trans-3-(3-furyl) acrylamido]morphinan hydrochloride (1, TRK-820), was discovered by a new working hypothesis and showed neither aversion nor preference in the Conditioned Place Preference test.
Abstract: A new type of K-agonist, 17-cyclopropylmethyl-3, 14β-dihydroxy-4, 5α-epoxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan hydrochloride (1, TRK-820), was discoverd by a new working hypothesis. The "message-address concept" for opioid antagonists and the "accessory site" for general antagonists were applied to design TRK-820. A unique structural feature of TRK-820, which is different from other prototypical K-opioid receptor agonists, is the existence of the 4, 5-epoxymorphinan structure with a tyrosine-glysine moiety for endogenous opioid peptides such as dynorphins. TRK-820 exhibited high potency and high K-selectivity in guinea pig ileum (GPI) and mouse vas deferens (MVD) preparations. In the mouse acetic-acid-induced writhing model and mouse tail flick model of antinociception, TRK-820 was 85-140 times more potent than morphine and 85-350 times more potent than U-50488H. This structurally novel K-agonist showed neither aversion nor preference in the Conditioned Place Preference test, in spite of the fact that prototypes of K-agonists (U-50488H derivatives) demonstrated aversion.
162 citations
TL;DR: In this paper, the applicability of the modified Wilson model for calculating drug solubility in water-cosolvent mixtures is presented, and the accuracy and predictability of this model are compared with those of other models which calculate solute solubilities as a function of the solvent composition.
Abstract: Applicability of the modified Wilson model for calculating drug solubility in water-cosolvent mixtures is presented. The accuracy and predictability of the model are compared with those of other models which calculate solute solubility as a function of the solvent composition. Mean of percent deviations from experimental values are 7.77, 8.70, 9.06, 10.72, 10.72 and 18.71, for the modified Wilson, double-log exponential, general single model, combined nearly ideal binary solvent/Redlich-Kister, excess free energy and mixture response surface methods, respectively.
160 citations
TL;DR: It was understood that the use of a polymer with high compatibility and adhesion with nifedipine provides a high supersaturation level of the drug in dissolution, and the solubility parameter was found to be useful for selecting a suitable polymer as a component of combined carriers.
Abstract: The objective of this investigation was to clarify the influence of water-soluble polymers on the dissolution behavior of nifedipine from solid dispersions with combined carriers. All the solid dispersions of nifedipine were prepared by the fusion method using nicotinamide and 4 different water-soluble polymers, hydroxypropylmethylcellulose (HPMC), polyvinylpyrrolidone (PVP), partially hydrolyzed polyvinyl alcohol (PVA) and pullulan. HPMC, PVP or PVA dissolved in the fused liquid of nicotinamide and operated efficiently on the amorphous formation of nifedipine in solid dispersions. In dissolution studies, the drug concentration for these dispersions increased to more than twice intrinsic drug solubility. The rank order of the drug concentration was HPMC>PVP>PVA. However, since pullulan did not dissolve in the fused nicotinamide, nifedipine was present as a crystalline state in the solid dispersion; the supersaturation behavior of the drug was scarcely observed. The compatibility, namely, the solubility and miscibility, between nicotinamide or nifedipine and the polymers, was determined by differential scanning calorimetry using the mixtures treated with fusing and subsequent rapid cooling. Both HPMC and PVP exhibited high compatibility not only with nicotinamide but also with nifedipine. The crystallization behavior of nifedipine from a supersaturated solution containing nicotinamide or the polymers was studied. The inhibitory effect of HPMC or PVP for drug crystallization was evident, which would be related not to the solubilizing effect but to the adhesive force of the polymer for the drug. Therefore, it was understood that the use of a polymer with high compatibility and adhesion with nifedipine provides a high supersaturation level of the drug in dissolution. Further, the solubility parameter was found to be useful for selecting a suitable polymer as a component of combined carriers.
146 citations
TL;DR: The methanolic extract and ethyl acetate-soluble portion from a Brazilian natural medicine, the leaves of Myrcia multiflora DC, were found to show inhibitory activities on aldose reductase and alpha-glucosidase and on the increase of serum glucose level in sucrose-loaded rats and in alloxan-induced diabetic mice.
Abstract: The methanolic extract and ethyl acetate-soluble portion from a Brazilian natural medicine, the leaves of Myrcia multiflora DC., which has been used as a specific medicine against diabetes, were found to show inhibitory activities on aldose reductase and alpha-glucosidase and on the increase of serum glucose level in sucrose-loaded rats and in alloxan-induced diabetic mice. From the ethyl acetate-soluble portion, new flavanone glucosides, myrciacitrins I and II, and new acetophenone glucosides, myrciaphenones A and B, were isolated together with several known compounds such as five flavonol glycosides, myricitrin, mearnsitrin, quercitrin, desmanthin-1, and guaijaverin. The structures of new compounds were determined on the basis of physicochemical and chemical evidence. The principal components of this natural medicine including new glucosides, myrciacitrin I and myrciaphenone B, were found to show potent inhibitory activities on aldose reductase and alpha-glucosidase.
128 citations
TL;DR: The in vitro antimycotic activity of the 4',4"-OH and 2',2"-OH substituted compounds showed good activity than the other molecules in the two series.
Abstract: A series of 3-styryl-1, 5-diphenyl and 5-styryl-1, 3-diphenyl 2-pyrazolines of different substitutions has been synthesized by condensation of substituted α, β-unsaturated ketones with phenylhydrazine hydrochloride in presence of catalytic amount of concentrated HCl. Compounds in the 3-styryl series had OMe, NMe2, NO2, OH and isopropyl substituents and those in the 5-styryl series had OMe, NMe2 and NOs. The 3-styryl-1, 5-diphenyl compounds showed little variation in antibacterial activity towards gram-positive and gram-negative bacteria in terms of geometric mean minimum inhibitory concentrations (MIC). The 4', 4''-NMe2, 4', 4''-NO2 and 4', 4''-OMe compounds were found to possess the highest activity in the series. The 5-styryl-1, 3-diphenyl series showed lower activities than the 3-styryl series. The in vitro antimycotic activity of the 4', 4''-OH and 2', 2''-OH substituted compounds showed good activity than the other molecules in the two series.
120 citations
TL;DR: Results indicate that oleanolic acid 3-O-glucuronide and momordin Ic, given orally, have neither insulin-like activity nor insulin releasing-activity, and exhibit their hypoglycemic activity by suppressing the transfer of glucose from the stomach to the small intestine and by inhibiting glucose transport at the brush border of thesmall intestine.
Abstract: We examined the structure-related activity of oleanolic acid glycosides with respect to their inhibitory effect on the increase in serum glucose in oral glucose-loaded rats and their mechanism of action using oleanolic acid 3-O-glucuronide and momordin Ic. Both the 3-O-monodesmoside structure and 28-carboxyl group were confirmed to be essential for such activity, and the 3-O-glucuronide was more potent than 3-O-glucoside. On the other hand, the 28-ester glucoside moiety and 6'-methyl ester of the glucuronide moiety reduced such activity. Oleanolic acid 3-O-glucuronide and momordin Ic, both of which inhibited the increase in serum glucose in oral glucose-loaded rats, did not lower serum glucose in normal or intraperitoneal glucose-loaded rats, or alloxan-induced diabetic mice. These glycosides were found to suppress gastric emptying in rats, and also inhibit glucose uptake in the rat small intestine in vitro. These results indicate that oleanolic acid 3-O-glucuronide and momordin Ic, given orally, have neither insulin-like activity nor insulin releasing-activity. They exhibit their hypoglycemic activity by suppressing the transfer of glucose from the stomach to the small intestine and by inhibiting glucose transport at the brush border of the small intestine.
117 citations
TL;DR: In this paper, the structures of these new compounds were elucidated on the basis of their spectral data, and they were reported for the first time from a fungal source, Lentinus edodes, Flammulina velutipes, Hypsizigus marmoreus, Pleurotus ostreatus and Pholiota nameko together with fifteen known ones.
Abstract: Eight new sterols, 5α, 8α-epidioxy-(22E, 24R)-23-methylergosta-6, 22-dien-3β-ol (1), 3β, 5α, 9α-trihydroxy-(22E, 24R)-23-methylergosta-7, 22-dien-6-one (2), 3β, 5α, 9α-trihydroxy-(24S)-ergost-7-en-6-one (3), 3β, 5α, 9α, 14α-tetrahydroxy-(22E, 24R)-ergosta-7, 22-dien-6-one (4), (22E, 24R)-ergosta-7, 22-diene-3β, 5α, 6α, 9α-tetrol (5), 5α, 9α-epidioxy-3β-hydroxy-(22E, 24R)-ergosta-7, 22-dien-6-one (6), 5α, 9α-epidioxy-3β-hydroxy-(24S)-ergost-7-en-6-one (7) and 5α, 6α-epoxy-(22E, 24R)-ergosta-8, 22-diene-3β, 7β, 14α-triol (8), have been isolated from five edible mushrooms, Lentinus edodes, Flammulina velutipes, Hypsizigus marmoreus, Pleurotus ostreatus and Pholiota nameko together with fifteen known ones (9-23), of which two (16 and 17) are reported for the first time from a fungal source. The structures of these new compounds were elucidated on the basis of their spectral data.
TL;DR: Ten species used as Danshen resources showed good correlation between the AR inhibitory activity and the morphological classification, however, the intensities of their AR inhibitor activity varied, and they contained 1 in varying amounts, suggesting that the ten species were not the same, and thus their use as a DANShen resource should be based on their activity and/or active constituents.
Abstract: The dry root and rhizome of Salvia miltiorhiza (Lamiaceae) are used as a crude drug Danshen, while those of S. deserta (Xinjiang-Danshen) are mixed in Danshen at Xinjiang province when the former is in short supply. The water and MeOH extracts of S. deserta showed strong aldose reductase (AR) inhibitory activity, and their active constituents were determined to be polar compounds different from "tanshinones" of S. miltiorhiza, i.e., lithospermic acid B (1), salvianolic acid K (2), salviaflaside (3), and rosmarinic acid (4) (IC50, 2.63-3.91 microM). We also examined the AR inhibitory activity of water and MeOH extracts of seventeen Salvia plants, including ten species of Danshen resources (S. bowleyana, S. deserta, S. miltiorhiza, S. miltiorhiza var. miltiorhiza f. alba, S. paramiltiorhiza, S. paramiltiorhiza f. purpureo-rubra, S. przewalskii, S. przewalskii var. mandarinorum, S. sinica f. purpurea, S. trijuga), and their water extracts were also analyzed by liquid chromatography-mass spectrometry (LC-MS). The results indicated that there were four types with regard to the AR inhibitory activity and three types with regard to the amount of 1. Ten species used as Danshen resources showed good correlation between the AR inhibitory activity and the morphological classification. However, the intensities of their AR inhibitory activity varied, and they contained 1 in varying amounts. These facts suggested that the ten species were not the same, and thus their use as a Danshen resource should be based on their activity and/or active constituents.
TL;DR: This article examined the constitutents of the roots of Salvia deserta (Xinjiang-Danshen) and identified a new caffeic acid trimer [salvianolic acid K (1)], along with two known caesic acid dimers [salviaflaside (2), rosmarinic acid (3)], a known caffeIC acid tetramer [lithospermic acid B (4)], seven known abietane-type diterpenes [6, 7-dehydroroyleanone (5),
Abstract: Salvia deserta SCHANG. (Lamiaceae) is a plant grown in Xinjiang province in China, and its dried roots are called Xinjiang-Danshen. This plant has not been used as a medicine or a food, but recently it was reported that Xinjiang-Danshen is mixed in Dashen (roots of S. miltiorhiza BUNGE), a well-known Chinese crude drug, at Xinjiang province when latter was in short supply. We examined the constitutents of the roots of S. deserta (Xinjiang-Danshen) and identified a new caffeic acid trimer [salvianolic acid K (1)], along with two known caffeic acid dimers [salviaflaside (2), rosmarinic acid (3)], a known caffeic acid tetramer [lithospermic acid B (4)], seven known abietane-type diterpenes [6, 7-dehydroroyleanone (5), royleanone (6), taxodione (7), ferruginol (8), 7-O-methylhorminone (9), 7-O-acetylhorminone (10), horminone (11)], and a known steroid [daucosterol (12)].Five of the diterpenes (5, 6, 9-11) were "royleanones" and the main caffeic acid derivative was the trimer 1. These differed from the constituents of roots of S. miltiorhiza, which contains "tanshinones" as diterpenes and magnesium lithospermate B as the main caffeic acid derivative. Thus, the mixing of Xinjiang-Danshen with Danshen is not appropriate and two should be considered different drugs.
TL;DR: In this paper, seven new p-coumaric acid derivatives along with seventeen known compounds, including four flavonoids, one prenylated phenolic acid, four diterpenoic acids, one lignan, two p-paraphylactic acid esters and five cinnamic acid derivatives, were isolated from the ethyl acetate soluble fraction of 75% ethanol extract of Brazilian propolis.
Abstract: Seven new p-coumaric acid derivatives along with seventeen known compounds, including four flavonoids, one prenylated phenolic acid, four diterpenoic acids, one lignan, two p-coumaric acid esters and five cinnamic acid derivatives, were isolated from the ethyl acetate soluble fraction of 75% ethanol extract of Brazilian propolis. New compounds were elucidated as (E)-2, 3-dihydroconiferyl p-coumarate, (E)-3-{2, 3-dihydro-2-[2-[(E)-p-coumaroyloxy]-1-methylethyl]-5-benzofuranyl}-2-propenoic acid, (E)-4-(2, 3-dihydrocinnamoyloxy)cinnamic acid, (E)-3-(2, 2-dimethyl-3, 4-dihydro-3-hydroxy-2H-1-benzopyran-6-yl)-2-propenoic acid, (E)-3-[2, 3-dihydro-2-(1-methylethenyl)-5-benzofuranyl]-2-propenoic acid, (E)-3-[2, 3-dihydro-2-(1-methylethenyl)-7-prenyl-5-benzofuranyl]-2-propenoic acid and (E)-3-{3-[(E)-4-(2, 3-dihydrocinnamoyloxy)-3-methyl-2-butenyl]-4-hydroxy-5-prenylphenyl}-2-propenoic acid, on the basis of spectral evidence and chemical reaction. Five compounds : dihydrokaempferol (aromadendrin), 6-methoxykaempferol, 4-hydroxy-3-prenylbenzoic acid, plicatin B and capillartemisin A, were isolated from propolis for the first time.
TL;DR: The MeOH extract of the root and the ground part of Anthriscus sylvestris Hoffm showed a high inhibitory activity against MK-1, HeLa, and B16F10 cell growth in vitro.
Abstract: The MeOH extract of the root and the ground part of Anthriscus sylvestris HOFFM. showed a high inhibitory activity against MK-1, HeLa, and B16F10 cell growth in vitro. The activity was found only in the CHCl3-soluble fractions. From the CHCl3-soluble fraction of the root, falcarindiol, 1-(3'-methoxy-4', 5'-methylenedioxyphenyl)-1ξ-methoxy-2propene, elemicin, and nemerosin were newly isolated in addition to deoxypodophyllotoxin (anthricin), anthriscusin, (-)-deoxypodorhizone, and anthriscinol methyl ether which were reported earlier as constituents of the root of this plant.From the CHCl3-soluble fraction of the ground part, deoxypodophyllotoxin, (-)-deoxypodorhizone, nemerosin, and falcarindiol were isolated.In vitro antiproliferative activities of the isolates against MK-1, HeLa, and B16F10 cells are reported.
TL;DR: The extract of Viticis Fructus appeared to have an analgesic effect, and was subjected to activity-guided separation using acetic acid-induced writhing in mice, and the analgesia of some related iridoid glucosides is discussed.
Abstract: The extract of Viticis Fructus appeared to have an analgesic effect, and was subjected to activity-guided separation using acetic acid-induced writhing in mice. The active fraction gave new compounds, vitexfolin A (1A), B and C, 10-O-vanilloylaucubin (3), dihydrodehydrodiconiferylalcohol-beta-D- (2'-O-p-hydroxybenzoyl)glucoside (4), and vanilloyl-beta-D-(2'O-p-hydroxybenzoyl)glucoside, together with agnuside (2) and erythro- and threoguaiacylglycerols. Compounds 1A and 2-4 showed significant writhing inhibition following oral administration at doses of 15, 50, 25, and 50 mg/kg, respectively. The effect on pressure pain threshold was tested using compounds 1A and 2 at a dose of 50 mg/kg, and only the former produced the analgesia. The analgesic effect of some related iridoid glucosides is also discussed.
TL;DR: Based on their contents in the fresh and dried plant, calanthoside may be a common genuine glycoside of tryptanthrin, indirubin, and isatin in the plant.
Abstract: The methanolic extracts from Calanthe discolor LINDL. and C. liukiuensis SCHLTR. were found to exhibit hair restoring and skin blood flow promoting activities. Through bioassay-guided separation using the skin blood flow increasing effect, a novel indole S,O-bisdesmoside, calanthoside, was isolated together with three new components, glucoindican, calaliukiuenoside, and calaphenanthrenol, and known compounds such as tryptanthrin, indirubin, isatin, and indican. The structures of the new compounds were determined on the basis of physicochemical and chemical evidence and they showed an activating effect on skin blood flow. In addition, it was found that enzymatic hydrolysis of calanthoside with beta-glucosidase furnished tryptanthrin together with a small amount of indirubin and isatin, whereas indirubin and isatin were obtained from calanthoside by acid hydrolysis. Based on their contents in the fresh and dried plant, calanthoside may be a common genuine glycoside of tryptanthrin, indirubin, and isatin in the plant.
TL;DR: It is concluded from experimental results that AC and ME may be useful as enhancers for increasing drug permeation through the human nail plate for in vitro permeation of a hydrophilic model drug.
Abstract: The enhancing effects of various vehicles on the in vitro permeation of a hydrophilic model drug, 5-fluorouracil (5-FU), or a lipophilic model drug, tolnaftate (TN), through human nail plates were investigated using a modified side-by-side diffusion cell. Tip pieces from the 5th finger-nail, clipped from healthy volunteers, were used in this permeation study. The swelling and softening properties of the nail pieces were also measured in each vehicle. The weights and stresses of the nail pieces were dramatically changed after immersion in aqueous solvents containing N-acetyl-L-cysteine (AC) or 2-mercaptoethanol (ME). However, no significant change in the physicochemical properties of the nail pieces was found in the lipophilic vehicles. Thus, the water content in the nail plates absorbed from vehicles may relate to their physicochemical properties. Although keratin-softening agents and new skin permeation enhancers did not significantly promote 5-FU permeation compared with water alone, the flux from solvent systems containing AC or ME was substantially higher. In addition, TN permeation from solvents containing AC or ME could be measured, whereas that from other solvents was undetectable. When the AC concentration was increased, the 5-FU permeation and the nail weight increased and the stress of each nail piece decreased. It is concluded from these experimental results that AC and ME may be useful as enhancers for increasing drug permeation through the human nail plate.
TL;DR: TAN-67 was a potent delta-opioid receptor agonist that was shown to have antinociceptive activity following subcutaneous administration in the mouse acetic acid abdominal constriction assay that was antagonized by NTI and 7-benzylidinenaltrexone but not by naltriben (delta 2-antagonist).
Abstract: We designed highly selective non-peptide agonists for the δ-opioid receptor. On the basis of the "message-address" concept in this field and the accessory site hypothesis, a novel class of hetericycle-fused octahydroisoquinoline derivatives were synthesized. One of these compounds (4aS*, 12aR*)-4a-(3-hydroxyphenyl)-2-methyl-1, 2, 3, 4, 4a, 5, 12, 12a-octahydropyrido[3, 4-b]acridine, TAN-67 (2)] showed high selectivity for the δ-opioid receptor (Ki=1.12 nM) in guinea-pig cerebrum with a 2070-fold lower affinity for the μ-opioid receptor and a 1600-fold lower affinity for the К-opioid receptor. TAN-67 was a potent δ-opioid receptor agonist with an IC50 value of 6.61 nM in the mouse vas deferens assay that was reversed by naltrindole (NTI) (Ke=0.21). Moreover, TAN-67 was shown to have antinociceptive activity following subcutaneous administration in the mouse acetic acid abdominal constriction assay that was antagonized by NTI (δ1-and δ2-antagonist) and 7-benzylidinenaltrexone (δ1-antagonist), but not by naltriben (δ2-antagonist). This systemically applicable non-peptide agonist will be useful for elucidating the pharmacological properties of the δ-opioid receptor.
TL;DR: From the water-soluble portion of the methanol extract of the herbal medicine fennel, the fruit of Foeniculum vulgare MILLER (Umbelliferae) as mentioned in this paper, four new phenylpropanoid glycosides, three new benzyl alcohol derivatives, one new phenylethanoid and its glycoside were obtained.
Abstract: From the water-soluble portion of the methanol extract of the herbal medicine fennel, the fruit of Foeniculum vulgare MILLER (Umbelliferae), four new phenylpropanoid glycosides, three new benzyl alcohol derivative glycosides, one new phenylethanoid and its glycoside were obtained. They were characterized by spectral investigation.
TL;DR: The significant contributor to the hydrotropic solubilization of nifedipine with nicotinamide was therefore the ligand hydrophobicity rather than the aromaticity of the pyridine ring.
Abstract: Nicotinamide is a hydrotropic agent that has been demonstrated to solubilize a wide variety of drugs through complexation. Past investigations on the potential interaction of nicotinamide with a solubilized drug have inadequately focused on aliphatic hydrotropes. This study examined the mechanism for the hydrotropic solubilization of nifedipine, a poorly water-soluble drug, in the aqueous solution of nicotinmide using not only nicotainamide analogues but also urea analogues as aliphatic hydrotropes. The values of stability constants, K1 : 1 and K1 : 2, at different temperatures in nicotinamide solution were determined by the phase solubility technique, and were utilized to estimate the thermodynamic parameters of complex formation between nifedipine and nicotinamide. The enthalpy change values suggested the participation of intermolecular forces other than hydrogen bonding in complexation. The aqueous solubility of nifedipine was measured in the presence of nicotinamide, urea and their analogues : N-methylnicotinamide, N, N-diethylnicotinamide, nipecotamide, methylurea, ethylurea and butylurea. The drug solubility increased in proportion to the amount of alkyl substituent on the amide nitrogen, and the solubilizing effect of butylurea was as high as that of nicotinamide. Furthermore, the relationship between the logarithmic drug solubilities in 1.0 M aqueous solutions of nicotinamide or urea analogues versus the logarithmic octanol-water partition coefficient values of ligands as an indication of hydrophobicity was found to be linear. The significant contributor to the hydrotropic solubilization of nifedipine with nicotinamide was therefore the ligand hydrophobicity rather than the aromaticity of the pyridine ring.
TL;DR: Three cardenolide glycosides obtained as the cytotoxic principles of "akond mul" showed similar cell line selectivity to those of cardiac glycoside such as digoxin and ouabain: they are toxic to cell lines of human origin, but not to those from mouse at 2 micrograms/ml.
Abstract: Three cardenolide glycosides, calotropin (1), frugoside (2), and 4'-O-β-D-glucopyranosylfrugoside (3), were obtained as the cytotoxic principles of "akond mul" (roots of Calotropis gigantea L.). The cytotoxicity of these compounds against various cell lines of human and mouse origin was tested. They showed similar cell line selectivity to those of cardiac glycosides such as digoxin and ouabain : they are toxic to cell lines of human origin, but not to those from mouse at 2μg/ml.
TL;DR: Martefragin A (1), a novel indole alkaloid, showed inhibitory activity on NADPH-dependent lipid peroxidation in rat liver microsomes and the structure of 1 was elucidated on the basis of spectral analysis of its methyl ester.
Abstract: Martefragin A (1), a novel indole alkaloid, was isolated from a red alga, Martensia fragilis, by repeated column chromatography. The structure of 1 was elucidated on the basis of spectral analysis of its methyl ester (2), including 1H- and 13C-NMR, 1H-1H correlation spectroscopy (COSY), and 13-1H COSY. A single crystal X-ray analysis of the hydrochloride of 1 confirmed the assignment. Martefragin A (1) showed inhibitory activity on NADPH-dependent lipid peroxidation in rat liver microsomes. The IC50 values of 1, α-tocopherol and ascorbic acid were 2.8, 87 and 200 μM, respectively.
TL;DR: New acylated polyhydroxyoleanene triterpene oligoglycosides, escins IIIb, IV, V, and VI and isoescins Ia, Ib, and V, were isolated from the seeds of horse chestnut tree.
Abstract: New acylated polyhydroxyoleanene triterpene oligoglycosides, escins IIIb, IV, V, and VI and isoescins Ia, Ib, and V, were isolated from the seeds of horse chestnut tree (Aesculus hippocastanum L.). Their structures were elucidated on the basis of chemical and physicochemical evidence.
TL;DR: The methanolic extract and 1-butanol-soluble fraction of American ginseng, the roots of Panax quinquefolium L., were found to exhibit a protective effect on liver injury induced by D-galactosamine and lipopolysaccharide.
Abstract: The methanolic extract and 1-butanol-soluble fraction of American ginseng, the roots of Panax quinquefolium L., were found to exhibit a protective effect on liver injury induced by D-galactosamine and lipopolysaccharide. Five new dammarane-type triterpene oligoglycosides called quinquenosides I, II, III, IV, and V were isolated together with fourteen known dammarane-type triterpene oligoglycosides such as chikusetsusaponin IVa, pseudo-ginsenoside-RC1, malonyl-ginsenoside-Rb1, and notoginsenosides-A,-C, and -K from the 1-butanol-soluble fraction. From the ethyl acetate-soluble fraction, four known acetylenic compounds and 6'-O-acetyl ginsenoside-Rg1 were isolated. The structures of quinquenosides I, II, III, IV, and V were determined on the basis of chemical and physicochemical evidence as 3-O-[6-O-(E)-2-butenoyl-beta-D-glucopyranosyl(1-->2)-beta-D- glucopyranosyl]-20-O-(beta-D-glucopyranosyl) 20(S)-protopanaxadiol (quinquenoside I), 3-O-[6-O-(E)-2-octenoyl-beta-D- glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-20-O-[beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl] 20(S)-protopanaxadiol (quinquenoside II), 3-O-[beta-D-glucopyranosyl (1-->2)-6-O-acetyl-beta-D-glucopyranosyl]-20-O-(beta-D-glucopyranosyl) 20(S)-protopanaxadiol (quinquenoside III), 3-O-[beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-20-O-beta-D- glucopyranosyl(1-->6)-beta-D-glucopyranosyl]-3 beta, 7 beta, 20(S)-trihydroxydammar-5,24-diene (quinquenoside IV), and 3-O-[beta-D-glucopyranosyl(1-->2)-beta-D-glucopyranosyl]-20-O-[alpha-D- glucopyranosyl(1-->4)-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranosyl ] 20(S)-protopanaxadiol (quinquenoside V).
TL;DR: Four new pyrrolidine alkaloids were isolated from the branches of Broussonetia kazinoki SIEB, (Moraceae) by spectroscopic and chemical methods.
Abstract: Two new pyrrolidine alkaloids, broussonetines G and H, were isolated from the branches of Broussonetia kazinoki SIEB. (Moraceae). Broussonetines G and H were formulated as 2 beta-hydroxymethyl-3 alpha, 4 beta-dihydroxy-5 alpha-(1-hydroxy- 6:10;10:13-diepoxytridecyl)-pyrrolidine (1) and 2 beta-hydroxymethyl-3 alpha, 4 beta-dihydroxy-5 alpha-(1-hydroxy- 5:9;9:13-diepoxytridecyl)-pyrrolidine (2), respectively, by spectroscopic methods. 1 and 2 inhibited beta-glucosidase, beta-galactosidase and beta-mannosidase.
TL;DR: The data show that human and rat liver fractions were more active than human duodenal mucosa and human blood leukocytes at hydrolysing the compounds, and the rank order of the compounds was, however, very similar in the different biological systems.
Abstract: One way to minimise systemic side effects of drugs is to design molecules, soft drugs, in such a way that they are metabolically inactivated rapidly after having acted on their pharmacological target. Hydrolases (esterases, peptidases, lipases, glycosidases, etc.) are enzymes well suited to use for drug inactivation since they are ubiquitously distributed. Insertion of ester bonds susceptible to enzymatic cleavage may represent one approach to make the action of a drug more restricted to the site of application. The present study describes the chemical synthesis of fourteen model compounds comprising a bicyclic aromatic unit connected by an ester-containing bridge to another aromatic ring. Initial attempts to define a) the tissue selectivity of the hydrolytic metabolism and b) the molecular structural factors affecting the rate of enzymatic ester cleavage are presented. The data show that human and rat liver fractions were more active than human duodenal mucosa and human blood leukocytes at hydrolysing the compounds. The rank order of the compounds was, however, very similar in the different biological systems. Commercially available pig liver carboxyl esterase and cholesterol esterase both reasonably well predict the rank order in the tissue fractions.
TL;DR: A series of novel thiazole-containing triazole antifungals showed potent and well-balanced in vitro activities and potent in vivo efficacy, and had a good safety profile.
Abstract: A series of novel thiazole-containing triazole antifungals was synthesized and evaluated for antifungal activity against a variety of clinically isolated pathogenic fungi in vitro and against systemic candidosis in vivo. These compounds showed potent antifungal activities in vitro and in vivo. In particular, (2R,3R)-3-[4-(4-cyanophenyl)thiazol-2-yl]-2-(2,4- difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol (12g; ER-30346) showed potent and well-balanced in vitro activities and potent in vivo efficacy, and had a good safety profile.
TL;DR: Two new naphthopyrones, cassiasides B2 and C2, were isolated from the seeds of Cassia obtusifolia and 2 was found to inhibit the histamine release from rat peritoneal exudate mast cells induced by antigen-antibody reaction.
Abstract: Two new naphthopyrones, cassiasides B2 (1) and C2 (2), were isolated from the seeds (Cassiae Semen) of Cassia obtusifolia L. The structures of the two new compounds 1 and 2 were established as rubrofusarin 6-O-beta-D- glucopyranosyl-(1-->6)-O-beta-D-glucopyranosyl-(1-->3)-O-beta-D- glucopyranosyl-(1-->6)-O-beta-D-glucopyranoside and toralactone 9-O-beta-D-glucopyranosyl-(1-->6)-O-beta-D-glucopyranosyl- (1-->3)-O-beta-D-glucopyranosyl-(1-->6)-O-beta-D-glucopyranoside, respectively, on the basis of spectral and chemical evidence. Compound 2 was found to inhibit the histamine release from rat peritoneal exudate mast cells induced by antigen-antibody reaction.
TL;DR: Two new series of fused aza-heteroarylbisphosphonates (5, 8), which are structurally quite different from incadronate (YM175), and related compounds were synthesized and evaluated for antiresorptive activity using a parathyroid hormone(PTH)-induced hypercalcemia model in rats (PIH model).
Abstract: Two new series of fused aza-heteroarylbisphosphonates (5, 8), which are structurally quite different from incadronate (YM175), and related compounds were synthesized and evaluated for antiresorptive activity using a parathyroid hormone (PTH)-induced hypercalcemia model in rats (PIH model). Among these compounds, several exhibited more potent antiresorptive activity than pamidronate. In particular, [1-hydroxy-2-(imidazo[1, 2-α]pyridin-3-yl)ethylidene]bisphosphonic acid (5b, minodronate) was 100-fold more potent than pamidronate in not only the PIH model, but also in an immobilization bone atrophy model in rats (DA model), and was selected for clinical development. The structure-activity relationships in these new series of bisphosphonates are discussed.