巻号一覧
63 巻, 4 号
選択された号の論文の10件中1～10を表示しています
- |<
- <
- 1
- >
- >|
Communication to the Editor
-
Kenichi Murai, Daisuke Endo, Norihito Kawashita, Tatsuya Takagi, Hirom ...2015 年 63 巻 4 号 p. 245-247
発行日: 2015/04/01
公開日: 2015/04/01
ジャーナル フリー HTML
電子付録A halogen-induced oxidative rearrangement of N,O-ketals prepared from cyclobutanones, leading to pyrrolidone derivatives, is developed. The reaction proceeds via an iminium ether intermediate and, depending on the reaction medium, two types of pyrrolidone derivative, containing a halogen atom or hydroxyl group, can be obtained.Graphical Abstract Fullsize Image抄録全体を表示PDF形式でダウンロード (493K) HTML形式で全画面表示
Regular Articles
-
Yuko Takasu, Miyako Yoshida, Mio Tange, Keiichi Asahara, Takahiro Uchi ...2015 年 63 巻 4 号 p. 248-254
発行日: 2015/04/01
公開日: 2015/04/01
ジャーナル フリー HTMLThe purpose of this study was to predict the stability of meropenem in a mixed infusion. The hydrolysis of meropenem in aqueous solution was found to be accelerated by pH, and by increasing concentrations of sodium bisulfite (SBS) and L-cysteine. Equations were derived for the degradation rate constants (kobs) of pH, SBS and L-cysteine, and fractional rate constants were estimated by the nonlinear least-squares method (quasi-Newton method using the solver in Microsoft Excel) at 25°C. The activation energy (Ea) and frequency factor (A) were calculated using the Arrhenius equation. The pH of the mixed infusion was estimated using the characteristic pH curve. From these results, an equation was derived giving the residual ratio (%) of meropenem at any time after mixing an infusion containing SBS and/or L-cysteine at any temperature, and in the pH range 4.0–10.0. A high correlation was shown to exist between the estimated and determined residual ratios (%).Graphical Abstract Fullsize Image抄録全体を表示PDF形式でダウンロード (1126K) HTML形式で全画面表示 -
Bingyu Zhang, Chao Lv, Weibo Li, Zhiming Cui, Dongdong Chen, Fangjun C ...2015 年 63 巻 4 号 p. 255-262
発行日: 2015/04/01
公開日: 2015/04/01
[早期公開] 公開日: 2015/02/11
ジャーナル フリー HTMLThis paper reported the synthesis, structure–activity relationship (SAR) and acaricidal activity in vitro against Psoroptes cuniculi, a mange mite, of 25 ethyl cinnamate derivatives. All target compounds were synthesized and elucidated by means of MS, 1H- and 13C-NMR analysis. The results showed that 24 out of 25 tested compounds at 1.0 mg/mL demonstrated acaricidal activity in varying degrees. Among them, 6, 15, 26, 27 and 30 showed significant activity with median lethal concentration values (LC50) of 89.3, 119.0, 39.2, 29.8 and 41.2 µg/mL, respectively, which were 2.1- to 8.3-fold the activity of ivermectin (LC50=247.4 µg/mL), a standard drug in the treatment of Psoroptes cuniculi. Compared with ivermectin, with a median lethal time value (LT50) of 8.9 h, 27 and 30 showed smaller LT50 values of 7.9 and 1.3 h, respectively, whereas 6, 15 and 26 showed slightly larger LT50 values of 10.6, 11.0 and 10.4 h at 4.5 µmol/mL. SARs showed that the presence of o-NO2 or m-NO2 on the benzene ring significantly improved the activity, whereas the introduction of a hydroxy, methoxy, acetoxy, methylenedioxy, bromo or chloro group reduced the activity. (E)-Cinnamates were more effective than their (Z)-isomer. Nevertheless, the carbon–carbon double bond in the acrylic ester moiety was proven not to be essential to improve the activity of cinnamic acid esters. Thus, the results strongly indicate that cinnamate derivatives, especially their dihydro derivatives, should be promising candidates or lead compounds for the development of novel acaricides for the effective control of animal or human acariasis.Graphical Abstract Fullsize Image抄録全体を表示PDF形式でダウンロード (590K) HTML形式で全画面表示 -
Yoshihisa Yamamoto, Toshiro Fukami, Tatsuo Koide, Yoshinori Onuki, Toy ...2015 年 63 巻 4 号 p. 263-272
発行日: 2015/04/01
公開日: 2015/04/01
[早期公開] 公開日: 2015/02/05
ジャーナル フリー HTML
電子付録The target of the present pharmaceutical study was the antipyretic analgesic, acetaminophen; its suppository form is usually split when used in pediatric patients. We focused on the active ingredient uniformity in these products, which were re-solidified after melting under high temperature condition. When sections of the cut surfaces of the seven acetaminophen suppository products (SUP-A–G) commercially available in Japan were visualized by polarized microscopy, acetaminophen crystals that were dispersed in the base were identified. The results of the quantitative determination of agent concentration for each cut portion (mg/g) suggested uniform dispersion of these crystals in the base of each product. The agent concentration in each portion of the suppositories that was re-solidified after melting at high temperatures was measured. Segregation of the active ingredient was observed in four products at a temperature of 40°C for 1 h, while active ingredient uniformity was maintained in the other three products (SUP-C, SUP-F and SUP-G). The latter three products also showed high viscosity at 40°C. At 50°C for 4 h, only the uniformity of the active ingredient in SUP-C was maintained. These results suggest that the uniformity of the active ingredient is lost in some acetaminophen suppositories that were re-solidified after melting under high temperature conditions. The degree of loss varies depending on the product.Graphical Abstract Fullsize Image抄録全体を表示PDF形式でダウンロード (10053K) HTML形式で全画面表示 -
Chisato Mukai, Katsuya Arima, Shuichi Hirata, Shigeo Yasuda2015 年 63 巻 4 号 p. 273-277
発行日: 2015/04/01
公開日: 2015/04/01
ジャーナル フリー HTML
電子付録The synthesis of a carbon analogue of scytonemin was accomplished on the basis of molybdenum-mediated intramolecular double Pauson–Khand type reaction of bis(allenyne), followed by the double aldol condensation of the formed double Pauson–Khand type adduct.Graphical Abstract Fullsize Image抄録全体を表示PDF形式でダウンロード (571K) HTML形式で全画面表示 -
Koichi Takao, Kaori Noguchi, Yosuke Hashimoto, Akira Shirahata, Yoshia ...2015 年 63 巻 4 号 p. 278-285
発行日: 2015/04/01
公開日: 2015/04/01
ジャーナル フリー HTMLA series of fatty acid amides were synthesized and their peroxisome proliferator-activated receptor α (PPAR-α) agonistic activities were evaluated in a normal rat liver cell line, clone 9. The mRNAs of the PPAR-α downstream genes, carnitine-palmitoyltransferase-1 and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, were determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) as PPAR-α agonistic activities. We prepared nine oleic acid amides. Their PPAR-α agonistic activities were, in decreasing order, N-oleoylhistamine (OLHA), N-oleoylglycine, Oleamide, N-oleoyltyramine, N-oleoylsertonin, and Olvanil. The highest activity was found with OLHA. We prepared and evaluated nine N-acylhistamines (N-acyl-HAs). Of these, OLHA, C16:0-HA, and C18:1Δ9-trans-HA showed similar activity. Activity due to the different chain length of the saturated fatty acid peaked at C16:0-HA. The PPAR-α antagonist, GW6471, inhibited the induction of the PPAR-α downstream genes by OLHA and N-oleoylethanolamide (OEA). These data suggest that N-acyl-HAs could be considered new PPAR-α agonists.Graphical Abstract Fullsize Image抄録全体を表示PDF形式でダウンロード (761K) HTML形式で全画面表示 -
Masayoshi Miyamoto, Taku Yamashita, Yuki Yasuhara, Akinori Hayasaki, Y ...2015 年 63 巻 4 号 p. 286-294
発行日: 2015/04/01
公開日: 2015/04/01
ジャーナル フリー HTMLCytochrome P450 reductase (CPR) is an important redox partner of microsomal CYPs. CPR is composed of a membrane anchor and a catalytic domain that contains FAD and flavin mononucleotide (FMN) as redox centers and mediates electron transfer to CYP. Although the CPR membrane anchor is believed to be requisite for interaction with CYP, its physiological role is still controversial. To clarify the role of the anchor, we constructed a mutant (Δ60-CPR) in which the N-terminal membrane anchor was truncated, and studied its effect on binding properties, electron transfer to CYP2C19, and drug metabolism. We found that Δ60-CPR could bind to and transfer electrons to CYP2C19 as efficiently as WT-CPR, even in the absence of lipid membrane. In accordance with this, Δ60-CPR could mediate metabolism of amitriptyline (AMT) and imipramine (IMP) in the absence of lipids, although activity was diminished. However, Δ60-CPR failed to metabolize omeprazole (OPZ) and lansoprazole (LPZ). To clarify the reason for this discrepancy in drug metabolism, we investigated the uncoupling reaction of the CYP catalytic cycle. By measuring the amount of H2O2 by-product, we found that shunt pathways were markedly activated in the presence of OPZ/LPZ in the Δ60-CPR mutant. Because H2O2 levels varied among the drugs, we conclude that the proton network in the distal pocket of CYP2C19 is perturbed differently by different drugs, and activated oxygen is degraded to become H2O2. Therefore, we propose a novel role for the membrane anchor as a suppressor of the uncoupling reaction in drug metabolism by CYP.Graphical Abstract Fullsize Image抄録全体を表示PDF形式でダウンロード (1077K) HTML形式で全画面表示
Notes
-
Sang Duk Han, Sang Won Jung, Sun Woo Jang, Hyuck Jun Jung, Miwon Son, ...2015 年 63 巻 4 号 p. 295-299
発行日: 2015/04/01
公開日: 2015/04/01
ジャーナル フリー HTMLIn order to enhance the dissolution rate of dronedarone hydrochloride (DRN), a novel soluplus® (polyethyleneglycol–polyvinyl caprolactam–polyvinyl acetate grafted copolymer)-based solid dispersion (SD) was formulated using a hot melt extrusion technique. The physical characteristics determined using scanning electron microscopy and X-ray powder diffraction, revealed that the active compound was molecularly dispersed in the amphiphilic polymer in a stable amorphous form. The dissolution rate of DRN from the tablet dosage form of SD extrudate consisted of the drug and Soluplus® in a weight ratio of 1 : 1, and was obviously more rapid and higher than that of the intact drug and marketed product (Multaq®, Sanofi, U.S.A.) at pH 1.2, 4.0 and 6.8. This suggests that Soluplus®-based SD formula can be a promising approach for enhancing the dissolution and oral absorption of DRN with a simple preparation process.Graphical Abstract Fullsize Image抄録全体を表示PDF形式でダウンロード (1513K) HTML形式で全画面表示 -
Yusuf Kemal Demir, Oya Kerimoglu2015 年 63 巻 4 号 p. 300-304
発行日: 2015/04/01
公開日: 2015/04/01
ジャーナル フリー HTMLHydrocolloid pectin formulation was utilized as a novel base for fabricating biodegradable micro-needle (MN) arrays. The pectin MNs were, on average, found to be 897.71±3.48 µm in height and 234.31±2.27 µm in base width, with an inter base spacing of 498.66±1.60 µm, and corresponding to an aspect ratio of 3.83±0.04. Bovine serum albumin (BSA) and pectin gel interaction was found to be dependent on the loaded protein amount. By contrast, regardless of the amount of BSA incorporated, pectin MNs competed with BSA to form a complex with Cu2+ ions in a bicinchoninic acid (BCA) kit. The glass transition of the pectin MN base was found to be 145.15±12.09, with a delta Cp of 2.60±0.02 J g−1 K−1. Because pectin MNs are skin friendly and naturally occurring, with biodegradable and hydrocolloidal features, they are promising vehicle for the controlled release of macromolecules.Graphical Abstract Fullsize Image抄録全体を表示PDF形式でダウンロード (1895K) HTML形式で全画面表示 -
Yi Li, Qinpei Lu, Jun Luo, Junsong Wang, Xiaobing Wang, Mengdi Zhu, Li ...2015 年 63 巻 4 号 p. 305-310
発行日: 2015/04/01
公開日: 2015/04/01
ジャーナル フリー HTMLSix new limonoids with modified furan ring, khaysenelide A–F (1–6), together with six known limonoids (7–12) were isolated from the stem bark of Khaya senegalensis. The basic skeletons of these new limonoids belong to mexicanolide (1, 2) and rearrangement phragmalin (3–6), which were elucidated on the basis of spectroscopic methods including high resolution-electrospray ionization (HR-ESI)-MS, one and two dimensional (1D and 2D)-NMR and confirmed by single-crystal X-ray crystallography using CuKα radiation of 1 and 3. Their absolute configurations were determined by the X-ray crystallography data and comparison of their electronic circular dichroism spectra. The inhibitory effect on nitric oxide (NO) production in lipopolysaccaride-activated RAW264.7 macrophages of new compounds was also tested.Graphical Abstract Fullsize Image抄録全体を表示PDF形式でダウンロード (720K) HTML形式で全画面表示
- |<
- <
- 1
- >
- >|