Cyclic peptides from marine organisms constitute a growing class of naturally occurring cytotoxic substances. A general synthetic method for thiazole amino acids, common components of these cyclic peptides 1-7, has been developed and total syntheses of 1-7 have been achieved. In the process, dolastatin 3 (1) with the proposed structure has been disclosed to differ from the natural material and the real structure 2 has been confirmed by its total synthesis. Patellamides (5) with the proposed structures have been revised to be 6 by their total syntheses. Absolute configuration of ascidiacyclamide (4) has been determined to be 4 and the structure of ulithiacyclamide (7) has been confirmed. Ulicyclamide (3) has been efficiently prepared in combination with solid and liquid phase syntheses. Didemnins A and B (9a and 9b), cyclic depsipeptides with potent antitumor activity, have been prepared by condensation of the key eastern and western fragments.
7-Aminoalkoxy-1-cyclopropyl-6-fluoro-1, 4-dihydro-4-oxoquinoline-3-carboxylic acid and their derivatives (8-10) were synthesized and their antibacterial activities were evaluated. Among them, compounds (10d-f, k) having an alkyl group at α-position of the amino group were found to have in vitro and in vivo antibacterial activity comparable to that of ciprofloxacin (1). Structure-activity relationship of these compounds was also stated.
A crude drug, Evodia fruit (goshuyu) was processed to detoxicate and reduce the bitter taste. Following the procedure described in Shokanron ( ?? ?? ?? ), Evodia fruit was washed in hot water, and then dried. The alkaloid contents of processed Evodia fruit was analyzed by high performance liquid chromatography. The result shows that the content of hydroxyevodiamine decreased to 0.55 times, while the content of rutaecarpine and evodiamine hardly change in the final processed material. However, evocarpine content increased to 1.3 times comparing with the untreated Evodia fruit. The phenomena was ascribed to the flowing-out of the water-soluble portion, and also the weight of extract and the intense of bitterness in the processed fruit were reduced to about 1/3 times.
Examination of the sizes of gastric mucosal injury has been conducted by visual means. However, the human visual-eye examination may sometimes involve personal biases and errors. In order to reduce these errors, automated analytical apparatuses have been developed. The equipment is generally expensive. In the present study, a low-cost imaging analytical method to examine the antiulcer action of drugs is reported. By using our imaging analytical method, an antiulcer effect of herbal medicine was examined on hydrochrolic acid-ethanol induced gastric mucosal injury. Acetone extract of Atractylodis Rhizoma was found to have antiulcer action. In addition, the examination of fractions of the acetone extract, obtained through column chromatography, indicated that atractylon, at 17.5mg/kg, p.o. significantly inhibits gastric mucosal injury.
The study on the first-pass metabolism of acetaminophen was carried out in normal and thyroxine-treated rats, administered 30mg/kg by three routes of intravenous, intraperitoneal, and oral one. Unconjugated acetaminophen and two major metabolites, glucuronide and sulfate in the plasma and urine were then measured 5 and 24 h after the administration, respectively. It was found that there was no difference in total percentage of excreted amount, independent of the routes for administration, between normal and thyroxine-treated rats. This fact shows that acetaminophen is absorbed completely from the gastrointestinal tract. However, it was also found that the extraction ratio of gastrointestinal tract in thyroxine-treated rats became smaller, and that the volume of distribution and total body clearance became larger than those in normal rats. The first-pass metabolism of acetaminophen was found to be influenced by the continuous administration of thyroxine.
Poly (vinylalcohol) (PVA) emulsion gel suppositories were prepared by a given cycle of freezing and thawing. Oil phase and emulsifying agent used were Panacete 800 and a series of Pluronic L-44, respectively. The effects of polymerization degree of PVA on the gel strength and the drug release were investigated. Drug release from PVA emulsion gel suppository was compared with that from a conventional suppository. The structure of gel was observed by using a scanning electron microscope. The gel strength increased when PVA emulsion gel suppository was prepared with Panacete 800 and Pluronic L-44. The drug release of hydrophilic and hydrophobic drugs from the suppository was in agreement with a zero-order release profile. When oil phase was added into PVA gel suppository, PVA fiber became thin and the network of PVA fiber became dense.
The radiation protective mechanisms on skin injury induced by soft X-irradiation were investigated by use of various radiation protective agents such as sulfur compounds (MEA, MEG, thiourea), nucleic acid constitutional compounds (adenosine, inosine), antioxidative compounds (sesamol, ferulic acid, ascorbic acid), crude drugs (Rosae Fructus, Anemarrhenae Rhizoma, Trapae Fructus, Forsythiae Fructus, Aloe arborescens). Scavenge action of activated oxygen, inhibitory effect of lipid peroxidation, inductoin of antioxidative protein and protective effect against damage of deoxyribonucleic acid and superoxide dismutase by X-irradiation were evaluated as the radiation protective mechanisms, and relationship between these results and protective effect of skin injury induced by radiation was studied.
In order to confirm the structure of three fecal metabolites, M-I, M-II and M-III, of a new calcium antagonist, (+)-3, 4-dihydro-2-[5-methoxy-2-[3-[N-methyl-N-[2-[(3, 4-methylenedioxy) phenoxyl] ethyl] amino] propoxy] phenyl]-4-methyl-3-oxo-2H-1, 4-benzothiazine (SD-3211), in rats, (+)-3, 4-dihydro-2-[5-hydroxy-2-[3-[N-methyl-N-[2-[(3, 4-methylenedioxy)-phenoxy] ethyl] amino] propoxy] phenyl]-4-methyl-3-oxo-2H-1, 4-benzothiazine ((+)-I), (+)-3, 4-dihydro-2-[5-hydroxy-2-[3-[N-[2-[(3, 4-methylenedioxy) phenoxy] ethyl] amino] propoxy]-phenyl]-4-methyl-3-oxo-2H-1, 4-benzothiazine ((+)-II) and (+)-3, 4-dihydro-2-[5-methoxy-2-[3-[N-[2-[(3, 4-methylenedioxy) phenoxy] ethyl] amino] propoxy] phenyl]-4-methyl-3-oxo-2H-1, 4-benzothiazine ((+)-III) were synthesized. Compounds (+)-I, (+)-II and (+)-III were identified with the fecal metabolites M-I, M-II and M-III, respectively. The calcium antagonistic activities of (+)-I, (+)-II and (+)-III were examined.
Inclusion complex of decanoic acid (DA) with α-cyclodextrin (α-CyD) was prepared as an additive of cefmetazole sodium (CMZ) suppository and rectally administered to rabbits. The resulting complexation was examined by the phase solubility method, differential scanning calorimetry (DSC) and X-ray diffractometry. Plasma concentration and AUC of CMZ after rectal administration of a suppository containing DA/α-CyD complex to rabbits increased more significantly than those with none additive.
Inhibitory effects of anthracyclines on bacterial collagenase were examined. Daunomycin, doxorubicin, and aclarubicin potently inhibited the collagenase, but mitomycin C and 5-fluorouracil did not inhibitit. Inhibitory activities of anthracyclines were constant regardless of the concentrations of Ca2+, activator of collagenase, or of Zn2+, active center of collagenase. These results suggest that the inhibitory mechanisms of anthracyclines were independent of a chelate effect on Ca2+ or Zn2+.
The metabolic studies on three types of chondroitin sulfates in rabbits were performed, The analyses of chondroitin sulfates gave the following results concerning their metabolic behavior. 1) Desulfation of chondroitin sulfates on GalNAc C6 position was observed more clearly after the administration of low molecular weight chondroitin sulfate (molecular weight, 6000 and 16000) than after that of high molecular weight one (molecular weight, 50000). 2) The disappearance velocities of the administered low molecular weight chondroitin sulfates in the blood and those of excretion into the urine were faster than those of high molecular weight one. 3) Intact chondroitin sulfates were excreted into the urine after the administration of low molecular weight chondroitin sulfates, while chondroitin sulfates having more than 30000 molecular weight were not detected in the collected urine after the administration of high molecular weight one.