Showing papers in "Chemical & Pharmaceutical Bulletin in 2000"
TL;DR: Electron spin resonance (ESR) spin trapping experiments revealed that eugenol and its dimer, having allyl groups in the structure, scavenged superoxide, and that only eugenoli trapped hydroxyl radicals under the conditions used, suggesting that e Eugenol and dieugenol have a different mechanism of antioxidation, i.e. eugenolin may inhibit lipid peroxidation at the level of initiation.
Abstract: This study was carried out to investigate the antioxidant activity of propofol (2,6-diisopropylphenol) and its related compounds, butylated hydroxyanisole (BHA), 2,6-dimethylphenol, 2,6-di-t-butylphenol, and their dimeric compounds. The degree of antioxidant activity was evaluated based on the degree of peroxidation induced with Fe-ascorbic acid in egg phosphatidylcholine through the determination of thiobarbituric acid-reactive substances (TBARS) formed during peroxidation. Their antioxidant activities were in the order of dipropofol>di(2,6-di-t-butylphenol)>diBHA>di(2,6-dimethylphenol). Dipropofol, a dimeric compound of propofol, showed the highest antioxidant activities. Dimeric compounds had higher activities than monomeric compounds, and the 1,1-diphenyl-p-picryhydrazyl-trapping ability of dimeric compounds was also greater than those of monomeric compounds (4-10-fold). These results suggest that dimeric phenols may increase their antioxidant activities along with increments in the conjugation system and play a inhibitory role in the propagation of free radical chain reactions.
235 citations
TL;DR: Six new highly oxygenated lanostane-type triterpenes were isolated from the spores of Ganoderma lucidum, together with known ganolucidic acid D and ganoderic acid C2, and the cytotoxicity of the compounds was carried out in vitro against Meth-A and LLC tumor cell lines.
Abstract: Six new highly oxygenated lanostane-type triterpenes, called ganoderic acid gamma (1), ganoderic acid delta (2), ganoderic acid epsilon (3), ganoderic acid zeta (4), ganoderic acid eta (5) and ganoderic acid theta (6), were isolated from the spores of Ganoderma lucidum, together with known ganolucidic acid D (7) and ganoderic acid C2 (8). Their structures of the new triterpenes were determined as (23S)-7beta,15alpha,23-trihydroxy-3,11-dioxolanosta-8, 24(E)-diene-26-oic acid (1), (23S)-7alpha,15alpha23-trihydroxy-3,11-dioxolanosta-8, 24(E)-diene-26-oic acid (2), (23S)-3beta3,7beta, 23-trihydroxy-11,15-dioxolanosta-8,24(E)-diene-26-oic acid (3), (23S)-3beta,23-dihydroxy-7,11,15-trioxolanosta-8, 24(E)-diene-26-oic acid (4), (23S)-3beta,7beta,12beta,23-tetrahydroxy-11,15-dioxolanos ta-8,24(E)-diene-26-oic acid (5) and (23S)-3beta,12beta23-trihydroxy-7,11,15-trioxolanosta-8,24(E )-diene-26-oic acid (6), respectively, by chemical and spectroscopic means, which included the determination of a chiral center in the side chain by a modification of Mosher's method. The cytotoxicity of the compounds isolated from the Ganoderma spores was carried out in vitro against Meth-A and LLC tumor cell lines.
227 citations
TL;DR: All the isolated compounds were tested for their cytotoxicity towards highly liver metastatic murine colon 26-L5 carcinoma cells, and the new diterpenes, except for 4, and flavonoids showed cytot toxicity with an ED50 value between 10 and 90 microg/ml.
Abstract: From the MeOH extract of the aerial part of Vietnamese Orthosiphon stamineus, five new isopimarane-type diterpenes [orthosiphols F-J (1-5)] and two new diterpenes [staminols A (6) and B (7)] with a novel carbon-framework, to which we proposed the name "staminane", and three new highly-oxygenated staminane-type diterpenes [staminolactones A (8) and B (9) and norstaminol A (10)] were isolated. Moreover, staminolactone A (8) is 8, 14-secostaminane-type and staminolactone B (9) is 13, 14-secostaminane-type, while norstaminol A (10) is 14-norstaminen-type. Together with these new diterpenes, sixteen known compounds were also isolated and identified to be : 7, 3', 4'-tri-O-methylluteolin (11), eupatorin (12), sinensetin (13), 5-hydroxy-6, 7, 3'4'-tetramethoxyflavone (14), salvigenin (15), ladanein (16), tetramethylscutellarein (17), 6-hydroxy-5, 7, 4'-trimethoxyflavone (18), vomifoliol (19), aurantiamide acetate (20), rosmarinic acid (21), caffeic acid (22), oleanolic acid (23), ursolic acid (24), betulinic acid (25), and β-sitosterol (26). All the isolated compounds were tested for their cytotoxicity towards highly liver metastatic murine colon 26-L5 carcinoma cells, and the new diterpenes, except for 4, and flavonoids (11, 12, 16, 18) showed cytotoxicity with an ED^ value between 10 and 90 μg/ml.
190 citations
TL;DR: Seven metabolites were isolated after anaerobic incubation of secoisolariciresinol diglucoside with a human fecal suspension and two bacterial strains, Peptostreptococcus sp.
Abstract: Seven metabolites were isolated after anaerobic incubation of secoisolariciresinol diglucoside (1) with a human fecal suspension. They were identified as (-)-secoisolariciresinol (2), 3-demethyl-(-)-secoisolariciresinol (3), 2-(3-hydroxybenzyl)-3-(4-hydroxy-3-methoxybenzyl)butane-1,4-diol (4), didemethylsecoisolariciresinol (5), 2-(3-hydroxybenzyl))-3-(3,4-dihydroxybenzyl)butane-1,4-diol (6), enterodiol (7) and enterolactone (8). Furthermore, two bacterial strains, Peptostreptococcus sp. SDG-1 and Eubacterium sp. SDG-2, responsible for the transformation of 1 to a mammalian lignan 7, were isolated from a human fecal suspension. The former transformed 2 to 3 and 5, as well as 4 to 6, and the latter transformed 5 to 6 and 7.
189 citations
TL;DR: This review gives the main results obtained by considering the classes of monodentate chiral ligands bearing one P(III) atom and involved in asymmetric catalysis with organometallic complexes.
Abstract: Chelating chiral diphosphines are often used as ligands of organometallic complexes. However monophosphines, or more generally ligands with one phosphorus linked to one or several heteroatom, may also be useful. This review gives the main results obtained in that area, by considering the classes of monodentate chiral ligands bearing one P(III) atom and involved in asymmetric catalysis with organometallic complexes.
153 citations
TL;DR: Two new phenolic compounds, glicophenone and glicoisoflavanone, were isolated from commercial licorice and their structures were elucidated on the basis of spectroscopic data, and it was suggested that 33 does not inhibit the formation of penicillin-binding protein 2' (PBP2'), but affects the enzymatic function of PBP2'.
Abstract: Two new phenolic compounds, glicophenone (1) and glicoisoflavanone (2), were isolated from commercial licorice, and their structures were elucidated on the basis of spectroscopic data. Antibacterial assays of licorice phenolics for Staphylococcus aureus, including four strains of methicillin-resistant S. aureus (MRSA), and also for Escherichia coli K12 and Pseudomonas aeruginosa PAO1, were then examined. Two compounds among them, 8-(gamma,gamma-dimethylallyl)-wighteone (21) and 3'-(gamma,gamma-dimethylallyl)-kievitone (28), showed remarkable antibacterial effects [minimum inhibitory concentrations (MICs), 8 microg/ml on the MRSA strains and methicillin-sensitive S. aureus. Licochalcone A (14), gancaonin G (20), isoangustone A (24), glyasperins C (30) and D (31), glabridin, (32), licoricidin (33), glycycoumarin (34) and licocoumarone (40) showed antibacterial effects on the MRSA strains with MIC values of 16 microg/ml. Effects on the beta-lactam resistance of the MRSA strains were also examined, and licoricidin (33) noticeably decreased the resistance of the MRSA strains against oxacillin, as shown by the reduction in the MICs of oxacillin (lower than 1/128-1/1000 in the presence of 8 microg/ml of 33, and 1/8-1/32 in the presence of 4 microg/ml of 33). Mechanistic study suggested that 33 does not inhibit the formation of penicillin-binding protein 2' (PBP2'), but affects the enzymatic function of PBP2'.
146 citations
TL;DR: Three new flavonoid glycosides, together with 15 known flavonoids, have been isolated from the leaves of Eriobotrya japonica, and characterized as (2S)- and (2R)-naringenin 8-C-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoides, and cinchonain Id 7-O-beta- D-glUCopyr
Abstract: Three new flavonoid glycosides, togethr with 15 known flavonoids, have been isolated from the leaves of Eriobotrya japonica, and characterized as (2S)- and (2R)-naringenin 8-C-α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranosides, and cinchonain Id 7-O-β-D-glucopyranoside, respectively, based on spectral analyses including two dimensional (2D) NMR techniques. Higher proanthocyanidin fraction in the water-soluble portion of the extract was characterized as a procyanidin oligomer mixture mainly composed of undecameric procyanidin. These polyphenols have also been assessed for cytotoxic activity against two human oral tumor (human squamous cell carcinoma and human salivary gland tumor) cell lines. Selective cytotoxicity of the procyanidin oligomer between tumor and normal gingival fibroblast cells, and its possible mechanism, were also described.
143 citations
TL;DR: In the process development of lovastatin using Aspergillus terreus DRCC 152 in solid state fermentation, a new butyrolactone-IV is isolated and the cytotoxic and antibacterial activities of these compounds were determined.
Abstract: In the process development of lovastatin using Aspergillus terreus DRCC 152 in solid state fermentation, we have isolated a new butyrolactone-IV (3) along with the previously reported butyrolactone-I (1) and butyrolactone-II (2) produced under submerged conditions The structure of compound 3 has been characterized as 3-hydroxy-5-[2-(1-hydroxy-1-methylethyl)-2(R)-2,3-dihydro-benzo[b]furan- 5 ylmethyl]-4-(4-hydroxyphenyl)-5-methoxycarbonyl-(5R)-2,5-dihydro-2 -furanone on the basis of spectroscopic studies The absolute stereochemistry has been determined by single crystal X-ray diffraction studies The cytotoxic and antibacterial activities of these compounds were determined
108 citations
TL;DR: A new chitinase inhibitor, designated as argadin (1), was isolated from the cultured broth of a fungal strain FO-7314 and arrested the moult of cockroach larvae upon injection into the ventral abdominal part.
Abstract: A new chitinase inhibitor, designated as argadin (1), was isolated form the cultured broth of a fungal strain FO-7314. The strain was identified as Clonostachys sp. from the morphological characteristics. Argadin was purified from the cultured mycelium by a combination of cation exchange, adsorption and gel filtration chromatographic methods. The structure of argadin was elucidated as cyclo(Nω-acetyl-L-arginyl-D-prolyl-homoseryl-histidyl-L-2-aminoadipyl) in which homoseryl γ-methylene bonded to histidyl α-amino residue. The IC50 value of argadin against Lucilia cuprina (blowfly) chitinase was 150 nM at 37°C and 3.4 nM at 20°C. Argadin arrested the moult of cockroach larvae upon injection into the ventral abdominal part.
102 citations
TL;DR: The phytochemical study of the aerial parts of Aster scaber Thunb.
Abstract: The phytochemical study of the aerial parts of Aster scaber THUNB. (Asteraceae) yielded a new caffeoyl quinic acid, (-) 3, 5-dicaffeoyl-muco-quinic acid (2) and three known compounds, (-) 3, 5-dicaffeoyl quinic acid (1), (-) 4, 5-dicaffeoyl quinic acid (3), (-) 5-caffeoyl quinic acid (4). The structures were established by high resolution spectroscopic methods. The antiviral effects against HIV-1 integrase of the compounds was evaluated. (-) 3, 5-Dicaffeoyl-muco-quinic acid (2) exhibited potent antiviral activity with an IC50 value of 7.0±1.3 μg/ml.
99 citations
TL;DR: The methanolic extract and ethyl acetate-soluble portion from the flowers of Chrysanthemum indicum L. were found to show inhibitory activity against nitric oxide (NO) production in lipopolysaccharide-activated macrophages.
Abstract: The methanolic extract and ethyl acetate-soluble portion from the flowers of Chrysanthemum indicum L., Chrysanthemi Indici Flos, were found to show inhibitory activity against nitric oxide (NO) production in lipopolysaccharide-activated macrophages. Five new germacrane-type sesquiterpenes, kikkanols D, D monoacetate, E, F, and F monoacetate, were isolated from the ethyl acetate-soluble portion. Their absolute stereostructures were elucidated on the basis of chemical and physicochemical evidence, which included application of the modified Mosher's method. The effects of fifteen principal components from the ethyl acetate-soluble portion of this medicinal flower against NO production were examined and, among them, acetylenic compounds and flavonoids were found to show potent inhibitory activity.
TL;DR: Six new furostanol-type steroid saponins called trigoneosides Xa, Xb, XIb, XIIa, XIIb, and XIIIa were isolated from the seeds of Egyptian Trigonella foenum-graecum L. (Leguminosae).
Abstract: Six new furostanol-type steroid saponins called trigoneosides Xa, Xb, XIb, XIIa, XIIb, and XIIIa were isolated from the seeds of Egyptian Trigonella foenum-graecum L. (Leguminosae) together with six known furostanol-type steroid saponins: trigoneosides Ia, Ib, and Va, glycoside D, trigonelloside C, and compound C. The structures of trigoneosides Xa, Xb, Xlb, XIIa, Xllb, and XIIIa were determined on the basis of chemical and physicochemical evidence as 26-O-beta-D-glucopyranosyl-(25S)-5alpha-furostane-2alpha+ ++,3beta,22xi,26-tetraol 3-O-alpha-L-rhamnopyranosyl(1-->2)-,beta-D-glucopyranoside, 26-O-beta-D-glucopyranosyl-(25R)-5alpha-furostane-2 alpha,beta,22xi,26tetraol 3-O-alpha-L-rhamnopyranosyl(l -->2)-beta-D-glucopyranoside, 26-O-beta-D-glucopyranosyl-(25R)-5alpha-furostane2alpha++ +,beta,22xi,26-tetraol 3-O-beta-D-xylopyranosyl(l -->4)-beta-D-glucopyranoside, 26-O-beta-D-glucopyranosyl-(25S)-furost-4-ene-3beta,22xi,26- triol 3-O-Ca-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranoside, 26-O-beta-D-glucopyranosyl-(25R)-furost-4-ene-3beta,22xi+ ++,26-triol 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranoside, and 26-O-beta-D-glucopyranosyl(25S)-furost-5-ene-3beta,22xi,26-t riol 3-O-alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl (1-->3)-beta-D-glucopyranosyl(1--4)]-beta-D-glucopyranoside, respectively.
TL;DR: Coacervation between chitosan and alginate was rapid, but the rate may be controlled with the addition of water miscible organic solvents, and acetone was the more promising solvent moderator.
Abstract: Chitosan-alginate polyelectrolyte complex (PEC) have been prepared in situ in beads and microspheres. This study examines the preparation of suitable chitosan-alginate coacervates for casting into homogeneous PEC films for potential applications in packaging, controlled release systems and wound dressings. Coacervation between chitosan and alginate was rapid, but the rate may be controlled with the addition of water miscible organic solvents. Compared with ethanol and PEG200, acetone was the more promising solvent moderator. Suspensions of fine, uniformly dispersed coacervates were produced by a dropwise addition of 0.25% w/v chitosan solution (solvent: 1: 1 v/v of 2% acetic acid and acetone) into 0.25% w/v sodium alginate solution in water under rapid agitation. The PEC films were transparent and flexible. They exhibited high permeability to water vapor, but resisted complete dissolution in 0.1 M HCI, distilled water and pH 7.4 phosphate buffer solution. Microscopic heterogeneity in the films could be reduced by immersion in aqueous media, but this was accompanied by modifications in the thickness, permeability and mechanical property of the films.
TL;DR: From the stem-bark of Juglans mandshurica, two new naphthalenyl glucopyranosides exhibited the most potent inhibition of reverse transcriptase (RT) activity, while the latter compound also inhibited ribonuclease H (RNase H) activity with an IC50 of 39 microM, comparable in potency to illimaquinone used as a positive control.
Abstract: From the stem-bark of Juglans mandshurica, two new naphthalenyl glucopyranosides, 1,4,8-trihydroxynaphthalene 1-O-[alpha-L-arabinofuranosyl-(1-->6)-beta-D-glucopyranoside] (1) and 1,4,8-trihydroxynaphthalene 1-O-beta-D-[6'-O-(3",5"-dihydroxy-4"-methoxybenzoyl)]glucopyranosi de (4), and two new alpha-tetralonyl glucopyranosides, 4 alpha,5,8-trihydroxy-alpha-tetralone 5-O-beta-D-[6'-O-(3",5"-dihydroxy-4"-methoxybenzoyl)]glucopyranosi de (7) and 4 alpha,5,8-trihydroxy-alpha-tetralone 5-O-beta-D-[6'-O-(3",4",5"-trihydroxybenzoyl)]glucopyranoside (8), were isolated together with three known naphthalenyl glucopyranosides (2, 3 and 5), one alpha-tetralonyl glucopyranoside (6), four flavonoids (9-12), and two galloyl glucopyranosides (13, 14). Amongst the isolated compounds, 1,2,6-trigalloylglucopyranose (13) and 1,2,3,6-tertagalloylglucopyranose (14) exhibited the most potent inhibition of reverse transcriptase (RT) activity with IC50 values of 0.067 and 0.040 microM, respectively, while the latter compound also inhibited ribonuclease H (RNase H) activity with an IC50 of 39 microM, comparable in potency to illimaquinone used as a positive control. 1,4,8-Trihydroxy-naphthalene 1-O-beta-D-glucopyranoside (2), 1,4,8-trihydroxynaphthalene 1-O-beta-D-[6'-O-(4"-hydroxy-3",5"-dimethoxybenzoyl)]glucopyranoside (3) and 8 showed moderate inhibition against both enzyme activities, and inhibitory potency of 2 against RNase H activity (IC50 = 156 microM) was slightly greater than that against the RT activity (IC50 = 290 microM). The inhibitory potencies of 4 alpha,5,8-trihydroxy-alpha-tetralone 5-O-beta-D-[6'-O-(4"-hydroxy-3",5"-dimethoxybenzoyl)] glucopyranoside (6), 7 and 8 against RT activity increased accompanied by an increase in the number of free hydroxyls on the galloyl residues, as represented by the IC50 values of > 500, 330 and 5.8 microM, respectively.
TL;DR: It is proposed that the structures of the new phytoalexins isolated from Avicennia marina are 1,2-naphthoquinones 8 and 9, named avicequinone-B and -C by Gillan and co-workers.
Abstract: Three new naphthoquinones and their analogues, named avicequinone-A (1), -B (2), -C (3), and avicenol-A (4), -B (5), -C (6), respectively, were isolated from the stem bark of Avicennia alba (Avicenniaceae) collected in Singapore, and their structures were elucidated by means of spectral methods. Gillan and co-workers have proposed that the structures of the new phytoalexins isolated from Avicennia marina are 1,2-naphthoquinones 8 and 9. Our synthetic and spectrometric studies showed that these structures should be revised respectively to 1,4-naphthoquinones 2 and 3, named avicequinone-B and -C by us.
TL;DR: The results indicated that capsule formulations should not be taken with drinks from the carbonated Cola-type, and gelatine containing capsules should preferably be administered with a warm drink, whereas HPMC capsules could be given with cold or warm drinks.
Abstract: The shell dissolution properties of gelatine, gelatine/polyethylene glycol (PEG) and hydroxypropyl methylcellulose (HPMC) capsules were studied as a function of temperature, dissolution medium, and after different storage conditions. In any dissolution medium with a pH below or equal to 5.8, HPMC capsule shells dissolved rapidly, and there was no difference in the time in which dissolution occurred in the tested temperature interval of 10 to 55°C. Gelatine and gelatine/PEG capsule shells, generally, did not dissolve at temperatures below 30°C. The shell dissolution time of all capsules tested was prolonged and more variable in mixed phosphate buffer pH=6.8. The addition of enzymes (pepsin, pancreatin) to any dissolution medium was found not to enhance the differences between the different types of capsules investigated. In practical terms, the results indicated that capsule formulations should not be taken with drinks from the carbonated Cola-type. Gelatine containing capsules should preferably be administered with a warm drink, whereas HPMC capsules could be given with cold or warm drinks. The latter type of capsules should also be preferred for preparations to be taken in the fasted state. A short storage of gelatine containing capsules under hot humid tropical conditions appeared not to alter the dissolution properties of the shells, and changes in disintegration times and dissolution times of formulations filled in such capsules might be a reflection of changes of the powders incorporated rather than of the capsule shells. However, a short storage of HPMC capsules under such conditions appeared to influence the capsule shell matrix.
TL;DR: The methanolic extract of parsley, apiin, and apigenin restored the uterus weight in ovariectomized mice when orally administered for consecutive 7 days and estrogenic activities of these flavones are nearly equal to those of the isoflavones.
Abstract: In the course of our screening for natural estrogenic compounds from Occidental medicinal herbs, the extracts of several herbs were found to show proliferative activity in MCF-7 (an estrogen-sensitive breast cancer cell line). Among these active herbs, the methanolic extract from the aerial parts of Petroselinum crispum (parsley) showed potent estrogenic activity, which was equal to that of isoflavone glycosides from soybean. Through bioassay-guided separation, we isolated several flavone glycosides and a new flavone glycoside, 6"-acetylapiin, with estrogenic activity together with a new monoterpene glucoside, petroside. The structures of 6"-acetylapiin and petroside were characterized by the chemical and physicochemical evidence. Estrogenic activities of these flavone glycosides were found to be enhanced by removal of their glycoside moieties. The EC50 values (concentration needed to enhance the MCF-7 proliferation 50% compared to non-estrogen treated cell) of their aglycones are as follows, apigenin (1.0 microM), diosmetin (2.9 microM), and kaempferol (0.56 microM). The estrogenic activities of these flavones are nearly equal to those of the isoflavones, daidzein (0.61 microM) and genistein (0.60 microM). The methanolic extract of parsley, apiin, and apigenin restored the uterus weight in ovariectomized mice when orally administered for consecutive 7 days.
TL;DR: The saponin mixture from the seeds of the tea plant was found to exhibit an inhibitory effect on gastric emptying and an accelerating effect on gastrointestinal transit in mice.
Abstract: Following the investigation of assamsaponins A, B, C, D, and E, four new saponins termed assamsaponins F, G, H, and I were isolated from the seeds of the tea plant (Camellia sinensis L. var. assamica PIERRE), while assamsaponin J was isolated from its leaves. The structures of assamsaponins F-J were elucidated on the basis of chemical and physicochemical evidence and found to be 16,22-O-diacetyl-21-O-angeloyltheasapogenol E 3-O-[beta-D-galactopyranosyl (1-->2)][beta-D-glucopyranosyl(1 -->2)- alpha-L-arabinopyranosyl(1-->3)]-beta-D-glucopyranosiduronic acid, 21-O-angeloyl-22-O-acetyltheasapogenol E 3-O-[beta-D-galactopyranosyl(1--> 2)][beta-D-glucopyranosyl(1-->2)-alpha-L-arabinopyranosyl(1-->3)]- beta-D-glucopyranosiduronic acid, 21-O-angeloyl-28-O-acetyltheasapogenol E 3-O-[beta-D-galactopyranosyl(1-->2)][beta-D-glucopyranosyl(1--> 2)-alpha-L-arabinopyranosyl(1-->3)]-beta-D-glucopyranosiduronic acid, 21-O-tigloyl-28-O-acetyltheasapogenol E 3-O-[beta-D-galactopyranosyl(1--> 2)][beta-D-glucopyranosyl(1--> 2)-alpha-L-arabinopyranosyl(1-->3)]-beta-D-glucopyranosiduronic acid, and 16,21-O-diacetyl-22-O-cinnamoyltheasapogenol B 3-O-[beta-D-galactopyranosyl(l-->2)][beta-D-rhamnopyranosy(1-->2)- alpha-L-arabinopyranosyl(1-->3)]-beta-D-glucopyranosiduronic acid, respectively. The saponin mixture from the seeds of the tea plant was found to exhibit an inhibitory effect on gastric emptying and an accelerating effect on gastrointestinal transit in mice. Theasaponin E1 the principle saponin of the tea plant, showed potent activity, while theasaponin E2 showed none, so that the position of the acyl groups in the sapogenin moiety is important from a pharmacological point of view.
TL;DR: A balance between adherence and detachment of the drug from the carrier surface was needed in order to optimize the delivery of a drug to the desired target sites using a dry powder inhaler.
Abstract: Application of the scanning probe microscopy technique for quantitative measurement of the surface roughness of lactose carriers was evaluated. The roughness values of four different lactose carriers were related to the in vitro deposition results of the drug, salbutamol sulphate. The rugosity values of the lactose carriers were represented by Ra values which were in the order of DCL-40>DCL-11>lactose 325M>lactose 200 M. In vitro deposition results using a twin impinger showed that rougher carrier surfaces generally allowed more drug particles to be emitted from the capsules and inhaler but the availability of the drug to stage 2 was reduced, as detachment of drug particles from the carrier surfaces was more hindered. There was an optimum Ra value for greater delivery of the drug particles to stage 2 of the twin impinger. A balance between adherence and detachment of the drug from the carrier surface was needed in order to optimize the delivery of a drug to the desired target sites using a dry powder inhaler.
TL;DR: Three new lignans, ficusal and ficusesquilignans A, B, B and one new gamma-lactone, ficusolide diacetate, were isolated from the wood of Ficus microcarpa L.f.
Abstract: Three new lignans, ficusal (1) and ficusesquilignans A (2), B (3) and one new γ-lactone, ficusolide diacetate (4), were isolated from the wood of Ficus microcarpa L.f. Their structures were determined by spectral evidence.
TL;DR: Compound 19a possessed good therapeutic efficacy against type II collagen-induced arthritis in DBA/1J mice with doses of 30 and 100 mg/kg, suggesting the development of 19a (designated T-614) as a prospective diseasemodifying antirheumatic agent.
Abstract: A group of derivatives of 7-methanesulfonylamino-6-phenoxychromone (1) at the pyrone and phenoxy rings was synthesized starting with 4-chloro-3-nitroanisole and evaluated against acute and chronic inflammations in oral administration in animals. Significant potency in the rat models of carrageenin-induced edema (CPE) and adjuvant-induced arthritis (AA) was realized with 29-fluoro and 29,49-difluoro derivatives (9a and 9d), and 3formylamino derivative (19a) and its 29-fluoro and 29,49-difluoro compounds (22a and 22d), displaying AA therapeutic effect of ED4052.5—7.1 mg/kg/d for 7 d and AA prophylactic effect of 53—70% inhibition at the dosage of 3 mg/kg/d for 22 d. To identify a candidate for further pharmacological study, the five compounds were subjected to evaluation of their gastro-ulcerogenic liability, leading to selection of the fluorine-free compound 19a which did not cause acute ulceration at 300 mg/kg in oral administration in rats. Compound 19a (ED4053.6 mg/kg in established AA) possessed good therapeutic efficacy against type II collagen-induced arthritis in DBA/1J mice with doses of 30 and 100 mg/kg, suggesting the development of 19a (designated T-614) as a prospective diseasemodifying antirheumatic agent. In addition, a preparative-scale synthetic route to T-614 has been established.
TL;DR: Two new compounds, paecilospirone and phomopsidin, and seven known compounds, have been isolated and characterized from marine-derived fungi collected in tropical and sub-tropical coral reef environments.
Abstract: Two new compounds, paecilospirone (1) and phomopsidin (2), and seven known compounds, chaetoglobosin A (3), griseofulvin (4), fusarielin A (5), fusapyrone (6), deoxyfusapyrone (7), and verrucarins J (8) and L acetate (9), have been isolated and characterized from marine-derived fungi collected in tropical and sub-tropical coral reef environments. The utility of marine-derived fungi as a source of bioactive secondary metabolites is discussed.
TL;DR: Two new ichthyotoxic compounds, aspidin PB and dryofragin (9), along with three known phloroglucinol derivatives (1-3) and five terpenoids, were isolated from the whole herbs of Dryopteris fragrans by toxicity-directed fractionation using Oryzias latipes.
Abstract: Two new ichthyotoxic compounds, aspidin PB (8) and dryofragin (9), along with three known phloroglucinol derivatives (1-3) and five terpenoids, were isolated from the whole herbs of Dryopteris fragrans by toxicity-directed fractionation using Oryzias latipes (Japanese name; medaka). The structures of the new compounds were determined by spectroscopic methods including 2D NMR techniques. Amongst the isolates, aspidin PB (8), dryofragin (9), and 1-5 exhibited potent ichthyotoxic activity against medaka with a median tolerance limit (TLm after 24 h) of 1.2-4.3 microg/ml. These compounds which are toxic to fish also had a potent inhibitory effect on the activation of Epstein-Barr virus early-antigen (EBV-EA) induced by tetradecanoyl phorbol 13-acetate, which is an in vitro short-term assay for anti-tumor promoting agents. Aspidin BB (2) and albicanol (4), which exhibited strong inhibitory effects on the EBV-EA activation, significantly suppressed an in vivo two-stage carcinogenesis on mouse skin.
TL;DR: The experimental model used is appropriate only at lower aging temperatures, while at higher ones the complexity of the system increases and molecular polymorphic arrangement could be involved, and the polymorphic form I formation is the one preferred.
Abstract: The purpose of this paper is to study the molecular mobility of paracetamol molecules in their amorphous state below the glass transition temperature (Tg) in order to evaluate the thermodynamic driving force which allows the amorphous form to recrystallize under different polymorphic modifications. Samples were aged at temperatures of -15, 0, 6, and 12 degrees C for periods of time from 1 h to a maximum of 360 h. The extent of physical aging was measured by a DSC study of enthalpy recovery in the glass transition region. The onset temperature of glass transition was also determined (Tg). Enthalpy recovery (deltaH) and change in heat capacity (deltaCp) were used to calculate the mean molecular relaxation time constant (tau) using the empirical Kohlausch-Williams-Watts (KWW) equation. Enthalpy recovery and onset glass transition temperature increased gradually with aging and aging temperatures. Structural equilibrium was reached experimentally only at an aging temperature of 12 degrees C (Tg-10 degrees C), according to the deltaH(infinity) results. The experimental model used is appropriate only at lower aging temperatures, while at higher ones the complexity of the system increases and molecular polymorphic arrangement could be involved. When structural equilibrium is experimentally reached, molecules can be arranged in their lowest energy state, and the polymorphic form I formation is the one preferred.
TL;DR: The inhibitory mechanism was proved directly by size exclusion chromatography to be inhibition of dimerization of the enzyme polypeptides and the ester bonds of the triterpene derivatives were found to be stable to lipase under mild alkaline conditions.
Abstract: Oleanolic acid derivatives with different lengths of 3-O-acidic acyl chains were synthesized and evaluated for their inhibitory activity against HIV-1 protease. The lengths of the acidic chains were optimized to 6 and 8 carbons. Changing a 3-ester bond to an amide bond or dimerization of the triterpenes retained their inhibitory activity against HIV-1 protease. Introduction of an additional acidic chain to C-28 of oleanolic acid increased the inhibitory activity appreciably, though a derivative with only one acidic chain linked at C-28 also showed potent activity against HIV-1 protease. The inhibitory mechanism was proved directly by size exclusion chromatography to be inhibition of dimerization of the enzyme polypeptides. The ester bonds of the triterpene derivatives were found to be stable to lipase under mild alkaline conditions.
TL;DR: Seven new monoterpene glycoside esters related to paeoniflorin were isolated from Paeoniae Radix together with polymeric proanthocyanidins, polygalloylglucoses and 48 known compounds by spectral investigation including two-dimensional NMR techniques.
Abstract: Seven new monoterpene glycoside esters related to paeoniflorin were isolaetd from Paeniae Radix, together with polymeric proanthocyanidins, polygalloylglucoses and 48 known compounds (a benzoylsucrose, seven aromatic acids, adenosine, nine monoterpene glycosids, eight flavan-3-ols, a catechin dimeer formed by oxidation, seven proanthocyanidins, three galloylsucroses, five galloylglucoses, and six ellagitannins). The structures of the new compounds were determined by spectral investigation including two-dimensional NMR techiniques. In addition, increased water solubility of polymeric proanthocyanidin in the presence of paeoniflorin was examined by n-octanol-water partition and 1H-NMR spectral experiments.
TL;DR: Pyrimidine analogs of potent RXR agonists (retinoid synergists) with a diphenylamine skeleton (DA series) exhibited potent retinoids synergistic activity in HL-60 cell differentiation assay and activated RXRs.
Abstract: Several pyridine- and pyrimidine-carboxylic acids were synthesized as ligand candidates for retinoid nuclear receptors, retinoic acid receptors (RARs) and retinoic X receptors (RXRs). Although the pyridine derivatives, 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carbamoyl]pyri dine-3-carboxylic acid (2b) and 6-[(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)carboxamido]py ridine-3-carboxylic acid (5b) are more potent than the corresponding benzoic acid-type retinoids, Am80 (2a) and Am580 (5a), the replacement of the benzene ring of Am580 (5a), Am555 (6a), or Am55 (7a) with a pyrimidine ring caused loss of the retinoidal activity both in HL-60 cell differentiation assay and in RAR transactivation assay using COS-1 cells. On the other hand, pyrimidine analogs (PA series, 10 and 11) of potent RXR agonists (retinoid synergists) with a diphenylamine skeleton (DA series, 8 and 9) exhibited potent retinoid synergistic activity in HL-60 cell differentiation assay and activated RXRs. Among the synthesized compounds, 2-[N-n-propyl-N-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)a mino]pyrimidine-5-carboxylic acid (PA013, 10e) is most active retinoid synergist in HL-60 assay.
TL;DR: It was found that the interaction of CDs with liposomes changes depending not only on the length of fatty acid chain of phospholipid but also the hydrophobicity and the cavity size of CD.
Abstract: The interaction of cyclodextrins (CDs) with L-alpha-dipalmitoyl phopsatidyl choline (DPPC), L-alpha-distearoyl phosphatidyl choline (DSPC), and L-alpha-dimyristoyl phosphatidyl choline (DMPC) unilamellar liposomes was investigated by the leakage of carboxylfluorescein (CF) entrapped in the inner aqueous phase of liposomes, at 25 degrees C (DPPC and DSPC liposomes) and at 5 degrees C (DMPC liposomes). The efficiency of CDs for CF leakage was remarkable in the order of heptakis (2,6-di-O-methyl)-beta-CD (DOM-beta-CD) > alpha-CD > heptakis (2,3,6-tri-O-methy)-beta-CD (TOM-beta-CD) from DPPC liposomes, in the order of DOM-beta-CD > TOM-beta-CD > alpha-CD from DSPC liposomes and in the order of alpha-CD > DOM-beta-CD > TOM-beta-CD from DMPC liposomes. The other CDs used in the present studies, beta-CD, 2-hydroxylpropyl beta-CD, and gamma-CD scarcely induced the CF leakage from above the three liposomes. From the profiles of % CF leakage, together with measurements of differential scanning calorimetry, it was found that hydrophobic DOM-beta-CD penetrates the matrix of the liposomes to interact with them as well as TOM-beta-CD, and that less hydrophobic alpha-CD exists at the surface of the membrane to interact with the liposomes. Further, it was found that the interaction of CDs with liposomes changes depending not only on the length of fatty acid chain of phospholipid (condensation force and hydrophobicity) but also the hydrophobicity and the cavity size of CD.
TL;DR: New bis-pyridine alkaloids, pyrinodemins B-D (1-3), have been isolated together with p Pyrinodemin A (4) and related 3-alkyl pyridineAlkaloids 5-8 from the Okinawan marine sponge Amphimedon sp.
Abstract: New bis-pyridine alkaloids, pyrinodemins B-D (1-3), have been isolated together with pyrinodemin A (4) and related 3-alkyl pyridine alkaloids 5-8 from the Okinawan marine sponge Amphimedon sp. and the structures were elucidated from spectroscopic data. Pyrinodemins B-D (1-3) showed potent cytotoxicity, while compounds 5-8 exhibited antimicrobial activity.
TL;DR: Among the derivatives, R-102557 (16R: Ar=4-(2,2,3,3-tetrafluoropropoxy)phenyl) showed excellent in vivo activities against Candida, Aspergillus and Cryptococcus species and showed high tolerance in a preliminary toxicity study in rats.
Abstract: Novel triazole compounds with a dioxane ring were synthesized. Condensation of the diol precursor 10 with various aromatic aldehydes 11-13 under acidic conditions afforded a series of dioxane-triazole compounds 14-16. The antifungal activities of the compounds 14-16 were evaluated in vivo in mice infection models against Candida and Aspergillus species. High activities were seen for the derivatives with one or two double bond(s) and an aromatic ring substituted with an electron-withdrawing group in the side chain. Among the derivatives, R-102557 (16R: Ar=4-(2,2,3,3-tetrafluoropropoxy)phenyl) showed excellent in vivo activities against Candida, Aspergillus and Cryptococcus species. It also showed high tolerance in a preliminary toxicity study in rats.