著者

樫原 宏 末宗 洋 常広 菜穂美 酒井 浄

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.38, no.9, pp.2581-2582, 1990-09-25 (Released:2008-03-31)

参考文献数

17

被引用文献数

2 3

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The enones (II), which were obtained from dimethyl 4, 5-isopropylidenedioxy-2-oxopentylphosphonate (Ia) and various aldehydes, were easily converted to 2-alkenylfurans (III) by treatment with p-TsOH in MeOH. In a similar manner, the furfuryl phosphonate (IVa) and the 3-methylfurfuryl phosphonate (IVb) were obtained from Ia and its 3-methylated analogue (Ib), respectively.

著者

樫原 宏 末宗 洋 藤本 勝彦 酒井 浄

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.37, no.10, pp.2610-2614, 1989-10-25 (Released:2008-03-31)

参考文献数

17

被引用文献数

7 9

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A new synthetic route to optically active α, β-, β', γ'-unsaturated alcohols was established. The chiral enones (6 and 8), prepared from dimethyl malate via chiral phosphonates (4 and 5), were diastereoselectively reduced with Zn(BH4)2 to afford the 1, 3-syn derivatives (9 and 11). As an application of this 1, 3-asymmetric induction, the fungitoxic C-18 hydroxy unsaturated fatty acid isolated from stromata of Epichloe typhina was synthesized.

著者

Kazuhiro Machida Yoichiro Hirose Shinichiro Fuse Tohru Sugawara Takashi Takahashi

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.58, no.1, pp.87-93, 2010-01-01 (Released:2010-01-01)

参考文献数

14

被引用文献数

26 36

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In this paper we describe the development of a fully-automated solution-phase synthesizer, ‘ChemKonzert’ that can be used to prepare a wide variety of organic compounds. The automated synthesizer is ingeniously designed to perform most of the chemical reactions currently used by synthetic organic chemists and utilizes a centrifugal separator to efficiently achieve liquid-liquid extraction. The design of the hardware and software will be described in this paper, and several examples of organic reactions will also be presented as applications of the apparatus.

著者

Yusuke Sato

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.12, pp.1141-1159, 2021-12-01 (Released:2021-12-01)

参考文献数

192

被引用文献数

12

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Considerable efforts have been made on the development of lipid nanoparticles (LNPs) for delivering of nucleic acids in LNP-based medicines, including a first-ever short interfering RNA (siRNA) medicine, Onpattro, and the mRNA vaccines against the coronavirus disease 2019 (COVID-19), which have been approved and are currently in use worldwide. The successful rational design of ionizable cationic lipids was a major breakthrough that dramatically increased delivery efficiency in this field. The LNPs would be expected to be useful as a platform technology for the delivery of various therapeutic modalities for genome editing and even for undiscovered therapeutic mechanisms. In this review, the current progress of my research, including the molecular design of pH-sensitive cationic lipids, their applications for various tissues and cell types, and for delivering various macromolecules, including siRNA, antisense oligonucleotide, mRNA, and the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) system will be described. Mechanistic studies regarding relationships between the physicochemical properties of LNPs, drug delivery, and biosafety are also summarized. Furthermore, current issues that need to be addressed for next generation drug delivery systems are discussed.

著者

Kenichi Kawano Fumiaki Yokoyama Kouhei Kamasaka Jun Kawamoto Takuya Ogawa Tatsuo Kurihara Shiroh Futaki

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.11, pp.1075-1082, 2021-11-01 (Released:2021-11-01)

参考文献数

38

被引用文献数

4

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Extracellular vesicles (EVs) have emerged as important targets in biological and medical studies because they are involved in diverse human diseases and bacterial pathogenesis. Although antibodies targeting the surface biomarkers are widely used to detect EVs, peptide-based curvature sensors are currently attracting an attention as a novel tool for marker-free EV detection techniques. We have previously created a curvature-sensing peptide, FAAV and applied it to develop a simple and rapid method for detection of bacterial EVs in cultured media. The method utilized the fluorescence/Förster resonance energy transfer (FRET) phenomenon to achieve the high sensitivity to changes in the EV amount. In the present study, to develop a practical and easy-to-use approach that can detect bacterial EVs by peptides alone, we designed novel curvature-sensing peptides, N-terminus-substituted FAAV (nFAAV) peptides. The nFAAV peptides exerted higher α-helix-stabilizing effects than FAAV upon binding to vesicles while maintaining a random coil structure in aqueous solution. One of the nFAAV peptides showed a superior binding affinity for bacterial EVs and detected changes in the EV amount with 5-fold higher sensitivity than FAAV even in the presence of the EV-secretory bacterial cells. We named nFAAV5, which exhibited the high ability to detect bacterial EVs, as an EV-sensing peptide. Our finding is that the coil–α-helix structural transition of the nFAAV peptides serve as a key structural factor for highly sensitive detection of bacterial EVs.

著者

Ryohei Aoyagi Takahiro Yamamoto Yuuki Furukawa Makoto Arita

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.10, pp.953-961, 2021-10-01 (Released:2021-10-01)

参考文献数

99

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Polyunsaturated fatty acids (PUFAs), esterified to phospholipids, are susceptible to oxidation. They form oxidized phospholipids (OxPLs) by oxygenases or reactive oxygen species (ROS), or both. These OxPLs are associated with various diseases, such as atherosclerosis, pulmonary injuries, neurodegenerative diseases, cancer, and diabetes. Since many types of OxPLs seem to be generated in vivo, precise determination of their structural diversity is required to understand their potential structure-specific functions. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful method to quantitatively measure the structural diversity of OxPLs present in biological samples. This review outlines recent advances in analytical methods for OxPLs and their physiological relevance in health and diseases.

著者

Norio Ogata Hideaki Tagishi Motonori Tsuji

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.68, no.12, pp.1193-1200, 2020-12-01 (Released:2020-12-01)

参考文献数

41

被引用文献数

3

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Anisakiasis is common in countries where raw or incompletely cooked marine fish are consumed. Currently, effective therapeutic methods to treat anisakiasis are unavailable. A recent study found that wood creosote inactivates the movement of Anisakis species. Essential oil of Origanum compactum containing carvacrol and thymol, which are similar to the constituents of wood creosote, was reported to inactivate Anisakis by inhibiting its acetylcholinesterase. We examined whether wood creosote can also inhibit acetylcholinesterase. We examined the effect of components of wood creosote using the same experimental method. A computer simulation experiment (molecular docking) was also performed. Here, we demonstrate that wood creosote inactivated acetylcholinesterase in a dose-dependent manner with an IC50 of 0.25 mg/mL. Components of wood creosote were also tested individually: 5-methylguaiacol, p-cresol, guaiacol, o-cresol, 2,4-dimethylphenol, m-cresol, phenol and 4-methylguaiacol inactivated the enzyme with an IC50 of 14.0, 5.6, 17.0, 6.3, 3.9, 10.0, 15.2 and 27.2 mM, respectively. The mechanism of acetylcholinesterase inactivation was analyzed using a computer-based molecular docking simulation, which employed a three-dimensional structure of acetylcholinesterase and above phenolic compounds as docking ligands. The simulation indicated that the phenolic compounds bind to the active site of the enzyme, thereby competitively blocking entry of the substrate acetylcholine. These findings suggest that the mechanism for the inactivation of Anisakis movement by wood creosote is due to inhibition of acetylcholinesterase needed for motor neuron activity.

著者

Ryosuke Kori Keigo Murakami Yoshitake Nishiyama Tatsuya Toma Satoshi Yokoshima

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.3, pp.278-280, 2021-03-01 (Released:2021-03-01)

参考文献数

24

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We disclose our studies on a copper-mediated reaction of alkynes with trimethylsilyl azide to afford nitriles, and proposed a reaction mechanism, which involves an iodoalkyne and an iodotriazole as intermediates.

著者

Nahoko Uchiyama Junko Hosoe Naoki Sugimoto Kyoko Ishizuki Tatsuo Koide Mika Murabayashi Naoto Miyashita Kengo Kobayashi Yoshinori Fujimine Toshiyuki Yokose Katsuya Ofuji Hitoshi Shimizu Takashi Hasebe Yumi Asai Eri Ena Junko Kikuchi Kohei Kiyota Kazuhiro Fujita Yoshinobu Makino Naoko Yasobu Yoshiaki Iwamoto Toru Miura Koji Mizui Katsuo Asakura Takako Suematsu Hitomi Muto Ai Kohama Takashi Goto Masu Yasuda Tomohiko Ueda Yukihiro Goda

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.7, pp.630-638, 2021-07-01 (Released:2021-07-01)

参考文献数

22

被引用文献数

4

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Recently, quantitative NMR (qNMR), especially 1H-qNMR, has been widely used to determine the absolute quantitative value of organic molecules. We previously reported an optimal and reproducible sample preparation method for 1H-qNMR. In the present study, we focused on a 31P-qNMR absolute determination method. An organophosphorus compound, cyclophosphamide hydrate (CP), listed in the Japanese Pharmacopeia 17th edition was selected as the target compound, and the 31P-qNMR and 1H-qNMR results were compared under three conditions with potassium dihydrogen phosphate (KH2PO4) or O-phosphorylethanolamine (PEA) as the reference standard for 31P-qNMR and sodium 4,4-dimethyl-4-silapentanesulfonate-d6 (DSS-d6) as the standard for 1H-qNMR. Condition 1: separate sample containing CP and KH2PO4 for 31P-qNMR or CP and DSS-d6 for 1H-qNMR. Condition 2: mixed sample containing CP, DSS-d6, and KH2PO4. Condition 3: mixed sample containing CP, DSS-d6, and PEA. As conditions 1 and 3 provided good results, validation studies at multiple laboratories were further conducted. The purities of CP determined under condition 1 by 1H-qNMR at 11 laboratories and 31P-qNMR at 10 laboratories were 99.76 ± 0.43 and 99.75 ± 0.53%, respectively, and those determined under condition 3 at five laboratories were 99.66 ± 0.08 and 99.61 ± 0.53%, respectively. These data suggested that the CP purities determined by 31P-qNMR are in good agreement with those determined by the established 1H-qNMR method. Since the 31P-qNMR signals are less complicated than the 1H-qNMR signals, 31P-qNMR would be useful for the absolute quantification of compounds that do not have a simple and separate 1H-qNMR signal, such as a singlet or doublet, although further investigation with other compounds is needed.

著者

Kenji Sugibayashi Mika Futaki Miyu Hashimoto Asuka Fukuhara Kengo Matsumoto Takeshi Oshizaka Shoko Itakura Hiroaki Todo

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.7, pp.639-645, 2021-07-01 (Released:2021-07-01)

参考文献数

28

被引用文献数

2

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The purpose of the present study was to evaluate whether iontophoresis (IP) accelerates the intradermal migration rate of medium molecular weight drugs. Sodium polystyrene sulfonate (PSA) and fluorescein isothiocyanate-dextran (FD) were used as model medium molecular weight acidic and non-electrolyte drugs, respectively. Low molecular weight acid and non-electrolyte drugs were also used for comparison. Drug-loaded excised split-layered skin (SL skin) was used in the experiment. SL skin was prepared using (i) whole skin was split once, (ii) the drug solution was applied on the lower skin, and (iii) the upper skin was layered onto the lower skin containing the drug solution as in the original skin. The effect of constant-current cathodal or anodal IP was applied to the SL skin, and the time course of the cumulative amount of drug migration from the SL skin through the dermis to the receiver was followed. In cases without IP and with anodal IP, the intradermal migration rates of medium molecular weight drugs were much lower than those of small molecules. The driving force for drug migration was thought to be simple diffusion through the skin layer. In contrast, cathodal IP significantly increased the intradermal migration rate of PSA not but of FD or low molecular weight drugs. This IP-facilitated migration of PSA was probably due to electrorepulsion. These results suggest that IP can be used to increase the intradermal migration of medium molecular weight charged drugs.

著者

Keita Yaginuma Shuichi Tanabe Hirokazu Sugiyama Manabu Kano

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.6, pp.548-556, 2021-06-01 (Released:2021-06-01)

参考文献数

22

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Soft sensors play a crucial role as process analytical technology (PAT) tools. They are classified into physical models, statistical models, and their hybrid models. In general, statistical models are better estimators than physical models. In this study, two types of standard statistical models using process parameters (PPs) and near-infrared spectroscopy (NIRS) were investigated in terms of prediction accuracy and development cost. Locally weighted partial least squares regression (LW-PLSR), a type of nonlinear regression method, was utilized. Development cost was defined as the cost of goods required to construct an accurate model of commercial-scale equipment. Eleven granulation lots consisting of three laboratory-scale, two pilot-scale, and six commercial-scale lots were prepared. Three commercial-scale granulation lots were selected as a validation dataset, and the remaining eight granulation lots were utilized as calibration datasets. The results demonstrated that the PP-based and NIRS-based LW-PLSR models achieved high prediction accuracy without using the commercial-scale data in the calibration dataset. This practical case study clarified that the construction of accurate LW-PLSR models requires the calibration samples with the following two features: 1) located near the validation samples on the subspace spanned by principal components (PCs), and 2) having a wide range of variations in PC scores. In addition, it was confirmed that the reduction in cost and mass fraction of active pharmaceutical ingredient (API) made the PP-based models more cost-effective than the NIRS-based models. The present work supports to build accurate models efficiently and save the development cost of PAT.

著者

Ryuichiro Suzuki Yoshihiro Uesawa Yoshihito Okada Takumi Horikawa Yui Okabe Masaki Aburada Kunio Takahashi Kaoru Kinoshita

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.2, pp.199-202, 2021-02-01 (Released:2021-02-01)

参考文献数

11

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The 13C-NMR spectral data for the 15-carbon flavonoid skeleton in eleven methoxyflavones isolated from Kaempferia parviflora (Zingiberaceae) were processed by principal component analysis (PCA). Based on the PCA score plots, the methoxyflavones were categorized into three groups according to their structural features. The cytotoxicities of the methoxyflavones toward 3T3-L1 murine preadipocyte cells were evaluated by 3-(4,5-dimethylthiazole-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTT) assay and found to differ according to structure. The relationship between the 13C-NMR chemical shifts of the methoxyflavones and their cytotoxicities was investigated using Pearson’s correlation analysis. The 13C-NMR signal at C-10, a quaternary carbon, was correlated with cytotoxicity. Based on these results, a structural design which lowers the 13C-NMR chemical shift at C-10 would be important for the development of cytotoxic compounds. Although quantitative structure–activity and structure–property relationships are well established paradigms for predicting trends among a series of compounds, quantitative property–activity relationships have been relatively unstudied. This approach offers a new strategy for directing structure–activity relationship research.

著者

Nahoko Uchiyama Junko Hosoe Naoki Sugimoto Kyoko Ishizuki Tatsuo Koide Mika Murabayashi Naoto Miyashita Kengo Kobayashi Yoshinori Fujimine Toshiyuki Yokose Katsuya Ofuji Hitoshi Shimizu Takashi Hasebe Yumi Asai Eri Ena Junko Kikuchi Kohei Kiyota Kazuhiro Fujita Yoshinobu Makino Naoko Yasobu Yuko Yamada Yoshiaki Iwamoto Toru Miura Koji Mizui Katsuo Asakura Takako Suematsu Ai Kohama Yukihiro Goda

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.1, pp.118-123, 2021-01-01 (Released:2021-01-01)

参考文献数

11

被引用文献数

8

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Quantitative NMR (qNMR) is applied to determine the absolute quantitative value of analytical standards for HPLC-based quantification. We have previously reported the optimal and reproducible sample preparation method for qNMR of hygroscopic reagents, such as saikosaponin a, which is used as an analytical standard in the assay of crude drug section of Japanese Pharmacopoeia (JP). In this study, we examined the absolute purity determination of a hygroscopic substance, indocyanine green (ICG), listed in the Japanese Pharmaceutical Codex 2002, using qNMR for standardization by focusing on the adaptation of ICG to JP. The purity of ICG, as an official non-Pharmacopoeial reference standard (non-PRS), had high variation (86.12 ± 2.70%) when preparing qNMR samples under non-controlled humidity (a conventional method). Additionally, residual ethanol (0.26 ± 0.11%) was observed in the non-PRS ICG. Next, the purity of non-PRS ICG was determined via qNMR when preparing samples under controlled humidity using a saturated sodium bromide solution. The purity was 84.19 ± 0.47% with a lower variation than that under non-controlled humidity. Moreover, ethanol signal almost disappeared. We estimated that residual ethanol in non-PRS ICG was replaced with water under controlled humidity. Subsequently, qNMR analysis was performed when preparing samples under controlled humidity in a constant temperature and humidity box. It showed excellent results with the lowest variation (82.26 ± 0.19%). As the use of a constant temperature and humidity box resulted in the lowest variability, it is recommended to use the control box if the reference ICG standard is needed for JP assays.

著者

Yuki Igarashi Miki Takahashi Tomoaki Tsutsumi Koichi Inoue Hiroshi Akiyama

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.3, pp.286-290, 2021-03-01 (Released:2021-03-01)

参考文献数

26

被引用文献数

6

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Monitoring analysis of 14 per- and polyfluoroalkyl substances (PFAS), 9-chlorohexadecafluoro-3-oxanonane-1-sulfonate (F-53B) and dodecafluoro-3H-4,8-dioxanonanoate (ADONA) in bottled drinking water, tea and juice samples was performed using LC coupled with tandem mass spectrometry (LC-MS/MS) and solid-phase extraction (SPE). In the electrospray negative ion mode, the limit of detection and limit of quantification (LOQ) values were 0.1 to 0.8 ng/mL and 0.2 to 1.6 ng/mL, respectively. The calibration curves were linear from LOQ to 50 ng/mL (r2 > 0.999). The SPE procedure (Presep PFC-II) was utilized for sample preparation and recovery rates for three standards (35, 70 and 140 ng/L) were 80.4–118.8% with relative standard deviation (RSD) ≤ 0.6%. Using the developed method, various samples (n = 54) from Japanese markets were investigated for PFAS and F-53B contamination, and values below the LOQ were observed. It is concluded that for monitoring products in the Japanese market, our method represents a significant improvement over complex techniques for the quantification of PFAS and related compounds from various foods.

著者

Masashi Tsuda Mai Akakabe Mika Minamida Keiko Kumagai Masayuki Tsuda Yuko Konishi Akira Tominaga Eri Fukushi Jun Kawabata

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.1, pp.141-149, 2021-01-01 (Released:2021-01-01)

参考文献数

31

被引用文献数

5

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Two highly potent cytotoxic 26-membered macrolides, isocaribenolide-I (1) and a chlorohydrin 2, together with known amphidinolide N (3), have been isolated from a free-swimming dinoflagellate Amphidinium species (KCA09053 and KCA09056 strains) collected off Iriomote Island, Japan. The structures of 1 and 2 were determined to be a congener of 3 with an isobutyl terminus and the chlorohydrin form of 3, respectively, by detailed analyses of spectroscopic data. The relative stereochemistries of 1 and 2 were elucidated by the conformational analyses based on NMR data.

著者

Yoshiko Furukawa Satoshi Okuyama Yoshiaki Amakura Atsushi Sawamoto Mitsunari Nakajima Morio Yoshimura Michiya Igase Naohiro Fukuda Takahisa Tamai Takashi Yoshida

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.69, no.1, pp.2-10, 2021-01-01 (Released:2021-01-01)

参考文献数

74

被引用文献数

7

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The elderly experience numerous physiological alterations. In the brain, aging causes degeneration or loss of distinct populations of neurons, resulting in declining cognitive function, locomotor capability, etc. The pathogenic factors of such neurodegeneration are oxidative stress, mitochondrial dysfunction, inflammation, reduced energy homeostatis, decreased levels of neurotrophic factor, etc. On the other hand, numerous studies have investigated various biologically active substances in fruit and vegetables. We focused on the peel of citrus fruit to search for neuroprotective components and found that: 1) 3,5,6,7,8,3′,4′-heptamethoxyflavone (HMF) and auraptene (AUR) in the peel of Kawachi Bankan (Citrus kawachiensis) exert neuroprotective effects; 2) both HMF and AUR can pass through the blood–brain barrier, suggesting that they act directly in the brain; 3) the content of AUR in the peel of K. Bankan was exceptionally high, and consequently the oral administration of the dried peel powder of K. Bankan exerts neuroprotective effects; and 4) intake of K. Bankan juice, which was enriched in AUR by adding peel paste to the raw juice, contributed to the prevention of cognitive dysfunction in aged healthy volunteers. This review summarizes our studies in terms of the isolation/characterization of HMF and AUR in K. Bankan peel, analysis of their actions in the brain, mechanisms of their actions, and trials to develop food that retains their functions.

著者

Kumiko Sakai-Kato Yuki Takechi-Haraya Tsukasa Chida Manami Okazaki Masato Kozaki

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.68, no.8, pp.791-796, 2020-08-01 (Released:2020-08-01)

参考文献数

26

被引用文献数

1

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Because of the complexity of nanomedicines, analysis of their morphology and size has attracted considerable attention both from researchers and regulatory agencies. The atomic force microscope (AFM) has emerged as a powerful tool because it can provide detailed morphological characteristics of nanoparticles both in the air and in aqueous medium. However, to our knowledge, AFM methods for nanomedicines have yet to be standardized or be listed in any pharmacopeias. To assess the applicability of standardization of AFM, in this study, we aimed to identify robust conditions for assessing the morphology and size of nanoparticles based on a polystyrene nanoparticle certified reference material standard. The spring constant of the cantilever did not affect the size of the nanoparticles but needed to be optimized depending on the measurement conditions. The size analysis method of the obtained images affected the results of the analyzed size values. The results analyzed by cross-sectional line profiling were independent of the measurement conditions and gave similar results to those from dynamic light scattering. It was indicated that approximately 100 particles are required for a representative measurement. Under the optimized conditions, there were no significant inter-instrument differences in the analyzed size values of polystyrene nanoparticles both in air and under aqueous conditions.

著者

Ayaka Harada Hiroyasu Tsutsuki Tianli Zhang Ruda Lee Kinnosuke Yahiro Tomohiro Sawa Takuro Niidome

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.68, no.4, pp.363-368, 2020-04-01 (Released:2020-04-01)

参考文献数

39

被引用文献数

6

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Poly(D,L-lactide-co-glycolic) acid (PLGA) is a synthetic copolymer that has been used to design micro/nanoparticles as a carrier for macromolecules, such as protein and nucleic acids, that can be internalized by the endocytosis pathway. However, it is difficult to control the intracellular delivery to target organelles. Here we report an intracellular delivery system of nanoparticles modified with bacterial cytotoxins to the endoplasmic reticulum (ER) and anti-inflammatory activity of the nanoparticles. Subtilase cytotoxin (SubAB) is a bacterial toxin in certain enterohemorrhagic Escherichia coli (EHEC) strains that cleaves the host ER chaperone BiP and suppresses nuclear factor-kappaB (NF-κB) activation and nitric oxide (NO) generation in macrophages at sub-lethal concentration. PLGA-nanoparticles were modified with oligo histidine-tagged (6 × His-tagged) recombinant SubAB (SubAB-PLGA) through a pH-sensitive linkage, and their translocation to the ER in macrophage cell line J774.1 cells, effects on inducible NO synthase (iNOS), and levels of tumor necrosis factor (TNF)-α cytokine induced by lipopolysaccharide (LPS) were examined. Compared with free SubAB, SubAB-PLGA was significantly effective in BiP cleavage and the induction of the ER stress marker C/EBP homologous protein (CHOP) in J774.1 cells. Furthermore, SubAB-PLGA attenuated LPS-stimulated induction of iNOS and TNF-α. Our findings provide useful information for protein delivery to macrophages and may encourage therapeutic applications of nanoparticles to the treatment of inflammatory diseases.

著者

落合 英二 岡本 敏彦

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.7, no.5, pp.556-559, 1959-07-20 (Released:2008-03-31)

被引用文献数

3 7

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The results of dehydrogenation of anhydroignavinol and oxidation of des-N-methyl-anhydroignavinol are discussed and tentative structures for anhydroignavinol and ignavine are presented.

著者

大野 雅二 藤田 かがり 中井 久雄 小林 進 井上 圭三 野島 庄七

出版者

公益社団法人日本薬学会

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.33, no.2, pp.572-582, 1985-02-25 (Released:2008-03-31)

参考文献数

21

被引用文献数

41 49

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Acetyl glyceryl ether phosphorylcholines (platelet-activating factors ; PAFs), their enantiomers, and their analogues were efficiently synthesized in a stereochemically unambiguous manner starting from D-and L-tartaric acids as chiral synthons. The enantiomer of C16-PAF (S-comfiguration) showed far less activity than the natural PAF (R-configuration), and the N-methylpiperidine and N-methylpyrrolidine analogues were found to possess much higher activity than natural C16-PAF.