著者

鈴木 久美子 藤本 治宏 山崎 幹夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.31, no.6, pp.2176-2178, 1983-06-25 (Released:2008-03-31)

参考文献数

13

被引用文献数

10 17

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Fasciculol E and F were identified as the toxic principles of Naematoloma fasciculare (Nigakuritake), a poisonous mushroom. These compounds caused paralysis and death in mice. The LD50 values of fasciculol E and F to mice were determined as 50 mg/kg and 168 mg/kg (i. p.), respectively.

著者

Takuya Murai Shohei Hamada Yusuke Kobayashi Takahiro Sasamori Takumi Furuta

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.9, pp.605-615, 2022-09-01 (Released:2022-09-01)

参考文献数

31

被引用文献数

1

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The preparation, optical resolution, and structural investigations of a series of axially chiral biaryl dicarboxylic acids bearing oxygen, sulfur, and selenium atoms were carried out. The crystal structures of sulfur- and selenium-containing derivatives revealed that the carboxy groups of these compounds are located in a co-planar geometry with the fused aromatic rings including the chalcogen atoms. These conformational controls were found to be achieved by chalcogen-bonding interactions between chalcogen atoms in the aromatic rings and oxygen atoms in the carboxy groups. Even in the case of a binaphthofuran derivative, in which the formation of chalcogen-bonding interactions was expected to be negligible, the carboxy groups were also found to be located in a co-planar geometry toward its fused cyclic rings. Natural bond orbital (NBO) analyses of these dicarboxylic acids indicated the formation not only for the chalcogen-bonding interactions for S and Se derivatives, but also the tetrel-bonding interactions between the oxygen atoms in the carboxy groups and the carbon atoms in the fused cyclic rings for all biaryl dicarboxylic acids. These tetrel-bonding interactions were thought to contribute to conformational control in the binaphthofuran derivative. Physical and chiroptical properties such as the racemization barriers and circular dichroism (CD) spectra of these biaryl dicarboxylic acids were also revealed.

著者

三村 務 前田 和宏 辻坊 裕 佐竹 幹雄 藤田 孝夫

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.30, no.4, pp.1508-1512, 1982-04-25 (Released:2008-03-31)

参考文献数

11

被引用文献数

5 5

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Octopus melanin obtained from ink bags of Octopus vulgaris CUVIER was found to inhibit gastric secretion in rats in the same way as that from Ommastrephes bartrami LESUEL. The molecular weight of this melanin fraction (which has an indole skeleton) was estimated to be over 200000 by gel filtration on Sephadex G-200, and the Octopus melanin fraction (Fr. OM) released several kinds of proteins in the presence of SDS. The chemical composition of Fr. OM was melanin pigment 79%, protein 17.5% and sugar 1.7%, so Fr. OM was considered to be a melanoprotein. Fr. OM significantly reduced gastric secretion in rats at the dose of 1 mg/kg, i.p., and also prevented both ulcer formation in pylorusligated rats and aspirin-induced ulcer.

著者

Jukiya Sakamoto Mariko Kitajima Hayato Ishikawa

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.9, pp.662-668, 2022-09-01 (Released:2022-09-01)

参考文献数

34

被引用文献数

4

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A number of alkaloids found in Mitragyna species belonging to the Rubiaceae family have been shown to have potent biological activity such as analgesic properties. Here, we report the asymmetric total syntheses of mitragynine, speciogynine, and 7-hydroxymitragynine, which are classified as corynantheine-type monoterpenoid indole alkaloids, isolated from Mitragyna speciosa. These syntheses were accomplished within 12 steps and in >11% total yield from commercial 3-(trimethylsilyl)propanal using an organocatalytic anti-selective Michael reaction and bioinspired transformations.

著者

Yu Mikame Yui Sakai Ryo Tahara Kinuka Doi Tsuyoshi Yamamoto Chikara Dohno Takayuki Shibata Asako Yamayoshi

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

pp.c22-00333, (Released:2022-07-28)

参考文献数

23

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Several psoralen-conjugated oligonucleotides (Ps-Oligos) have been developed as photo-crosslinkable oligonucleotides targeting DNA or RNA. To avoid potential off-target effects, it is important to investigate the selective photo-crosslinking reactivity of Ps-Oligos to DNA or RNA. However, the selectivity of these Ps-Oligos has not been reported in detail thus far. In this study, we evaluated the photo-crosslinking properties of two Ps-Oligos, 5’-Ps-Oligo and a novel Ps-Oligo containing 2’-O-{[(4,5’,8-trimethylpsoralen)-4’-ylmethoxy]ethylaminocarbonyl}adenosine (APs2-Oligo). Notably, 5’-Ps-Oligo preferentially crosslinked with DNA, whereas APs2-Oligo preferentially crosslinked with RNA. These results demonstrate the interesting crosslinking properties of Ps-Oligos, which will provide useful information for the molecular design of novel Ps-Oligos in future studies.

著者

Tadamasa Terai Huifeng Ren Go Mori Yoshihito Yamaguchi Tetsuhito Hayashi

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.50, no.7, pp.1007-1010, 2002 (Released:2002-07-01)

参考文献数

14

被引用文献数

32 32

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Stevioside is natural non-caloric sweetner isolated from Stevia rebaudiana BERTONI, which has been used as a non-caloric sugar substitute in Japan. Pezzuto et al. demonstrated that steviol shows a dose-dependent positive response in forward mutation assay using Salmonella typhimurium TM677 in the presence of metabolic activation system (Aroclor induced rat liver S9 fraction). Our studies were carried out to identify the genuine mutagenic active substance from among the eight steviol derivatives. Steviol indicate almost similar levels of mutagenicity under the presence of S9 mixture, as reported by Pezzuto et al. 15-Oxo-steviol was found to be mutagenic at the one tenth the level of steviol itself under the presence of S9 mixture. Interestingly, specific mutagenicity of the lactone derivative under the presence of S9 mixture was ten times lower than that of the lactone derivative without the addition of S9 mixture.

著者

Yanhua Zhang Hao Geng Junjie Zhang Kehan He

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.7, pp.469-476, 2022-07-01 (Released:2022-07-01)

参考文献数

59

被引用文献数

4

---

The development of structurally novel nucleoside analogues is an active area in medicinal chemistry, since these drugs have proven clinical efficacy for decades. Azanucleosides are nucleoside analogues in which the sugar moieties are composed of nitrogen-containing rings or chains. In recent years, many azanucleosides have demonstrated therapeutic potential. In this short review, we describe recent advancements in azanucleosides, which may translate in a better understanding of the molecular design, biological activity, structure–activity relationship, and their related mechanism of action. The information summarized in this paper should encourage medicinal chemists in their future efforts to create more potent and effective chemotherapeutic agents.

著者

Norihiro Togo Hirotaka Murase Jeongsu Lee Yosuke Taniguchi Shigeki Sasaki

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.7, pp.498-504, 2022-07-01 (Released:2022-07-01)

参考文献数

17

被引用文献数

1

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Due to the importance of the RNA chemical modifications, methods for the selective chemical modification at a predetermined site of the internal position of RNA have attracted much attention. We have developed functional artificial nucleic acids that modify a specific site of RNA in a site- and base-selective manner. In addition, the copper-catalyzed azide-alkyne cycloaddition (CuAAC) has been shown to introduce additional molecules on the alkynes attached to the pyridine ring. However, it was found that some azide compounds produced the cycloadduct in lower yields. Therefore, in this study, we synthesized the pyridinyl transfer group with the alkyne attached via a polyethylene glycol (PEG) linker with a different length and optimized its structure for both the transfer and CuAAC reaction. Three new transfer groups were synthesized by introducing an alkyne group at the end of the triethylene (11), tetraethylene (12) or pentaethylen glycol linker (13) at the 5-position of the pyridine ring of (E)-3-iodo-1-(pyridin-2-yl)prop-2-en-1-one. These transfer groups were introduced to the 6-thioguanine base in the oligodeoxynucleotide (ODN) in high yields. The transfer groups 11 and 12 more efficiently underwent the cytosine modification. For the CuAAC reaction, although 7 showed low adduct yields with the anionic azide compound, the new transfer groups, especially 12 and 13, significantly improved the yields. In conclusion, the transfer groups 12 and 13 were determined to be promising compounds for the modification of long RNAs.

著者

Miyuki Konya Shiho Arima Daiki Lee Masaki Ohtawa Kenta Shimoyama Takashi Fukuda Ryuji Uchida Hiroshi Tomoda Noriyuki Yamaotsu Nobutada Tanaka Tohru Nagamitsu

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.4, pp.261-268, 2022-04-01 (Released:2022-04-01)

参考文献数

19

被引用文献数

3

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Habiterpenol is a G2 checkpoint inhibitor isolated from the culture broth of Phytohabitans sp. 3787_5. Here, we report the synthesis of new habiterpenol analogs through the total synthesis process of habiterpenol and evaluating the analogs for G2 checkpoint inhibitory activity. We investigated two different synthetic approaches for total synthesis, with intramolecular conjugate addition and Ti(III)-mediated radical cyclization as key reactions. Although the former was unsuccessful, the latter reaction facilitated stereoselective total synthesis and determination of the absolute configuration of habiterpenol. The extension of these chemistries to a structure–activity relationship (SAR) study gave new habiterpenol analogs, which could not be derived from natural habiterpenol and only be synthesized by applying the total synthesis. Therefore, this study provides important insights into SAR studies of habiterpenol.

著者

Shinya Kimura Sota Mori Masashi Yokoya Masamichi Yamanaka

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.6, pp.443-447, 2022-06-01 (Released:2022-06-01)

参考文献数

41

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Urea derivatives 1 and 2, synthesized from adenosine, were designed as low-molecular-weight gelators. Hydrophobic groups have been introduced into all or part of the hydroxy groups of the hydrophilic ribose moiety of 1 and 2 to control the solvophilicity of the molecules and their aggregates. Compound 2 selectively formed supramolecular gels in halogenated solvents such as chloroform and 1,2-dichloroethane. The supramolecular gel of 2 and chloroform was thermally stable and its gel-to-sol phase transition temperature was higher than the boiling point of chloroform. The physical properties of the supramolecular gel were investigated by determining its viscoelastic properties using a rheometer. The supramolecular gel realized multiple stimuli-responsive reversible gel–sol phase transitions. The supramolecular gel showed reversible phase transition by repeated warming–cooling cycles accompanying with the gel–sol transitions. The supramolecular gel could undergo five repeated mechano-responsive gel–sol transitions. Gel-to-sol phase transition could also be achieved by adding various anions to the supramolecular gel, such as tetrabutylammonium fluoride. Regelation was realized by adding boron trifluoride etherate to the fluoride ion containing sol. Addition of methanol to the supramolecular gel also induced gel-to-sol phase transition. Regelation was realized by adding molecular sieves 4 Å to the suspension.

著者

Yuta Takamura Ken-ichi Morishita Shota Kikuzawa Masaki Watanabe Hiroki Kakuta

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.2, pp.146-154, 2022-02-01 (Released:2022-02-01)

参考文献数

28

被引用文献数

2

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Small-molecular drugs, which are generally inexpensive compared with biopharmaceuticals and can often be taken orally, may contribute to the Sustainable Development Goals (SDGs) adopted by the United Nations. We previously reported the retinoid X receptor (RXR) agonist 4-(ethyl(3-isobutoxy-4-isopropylphenyl)amino)benzoic acid (NEt-3IB, 1) as a small-molecular drug candidate to replace biopharmaceuticals for the treatment of inflammatory bowel disease. The previous synthetic method to 1 required a large amount of organic solvent and extensive purification. In line with the SDGs, we aimed to develop an environmentally friendly, inexpensive method for the large-scale synthesis of 1. The developed method requires only a hydrophobic ether and EtOH as reaction and extraction solvents. The product was purified by recrystallization twice to afford 99% pure 1 at 100 mmol scale in about 30% yield. The optimized process showed a 35-fold improvement of the E-factor (an index of environmental impact) compared to the original method. This work, which changes the solvent used to environmentally preferable ones based on the existing synthetic method for 1, illustrates how synthetic methods for small-molecular drugs can be adapted and improved to contribute to the SDGs.

著者

Seiya Ohki Miyu Kunimatsu Shingo Ogawa Hiroki Takano Tomomi Furihata Hiromi Shibasaki Akitomo Yokokawa

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.5, pp.375-382, 2022-05-01 (Released:2022-05-01)

参考文献数

27

被引用文献数

2

---

Evaluation of endogenous melatonin (MEL) secretion using its urinary metabolites is useful for the treatment of circadian rhythm sleep disorders. The primary melatonin metabolites excreted in the urine are 6-hydroxymelatonin (6-O-MEL) sulfate (S-O-MEL) and 6-O-MEL glucuronate, which result from sequential MEL metabolism by phases I and II drug metabolizing enzymes. To determine the accurate MEL secretion level, these urinary metabolites should be enzymatically deconjugated and converted into MEL. Furthermore, the use of LC–tandem mass spectrometry (LC–MS/MS) is preferable for the precision of this determination. Therefore, as part of our ongoing efforts to ultimately determine the level of MEL secretion, we herein aimed to develop an LC–MS/MS-based quantification method for 6-O-MEL and optimize deconjugation conditions. We determined the LC–MS/MS conditions of 6-O-MEL measurement and optimized the conditions of enzymatic reactions. The most efficient S-O-MEL deconjugation (102.1%) was achieved with Roche Glucuronidase/Arylsulfatase (from Helix pomatia) at 37 °C, pH-4.0 reaction buffer, and 60 min of reaction time. For human urine samples, the minimum amount of the enzyme required was 5944 units. Under these conditions, the accuracy and precision values of the 6-O-MEL determination (relative errors and standard deviation) were −3.60–−0.47% and <6.80%, respectively. Finally, we analyzed the total amount of MEL metabolites excreted in 24-h urine samples; it was 6.70–11.28 µg in three subjects, which is comparable with the values reported till date. Thus, we have established a new method of measuring the total 6-O-MEL in human urine samples using an LC–MS/MS coupled with the prerequisite deconjugation reaction.

著者

Taro Shimizu Yoshino Kawaguchi Hidenori Ando Yu Ishima Tatsuhiro Ishida

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.5, pp.341-350, 2022-05-01 (Released:2022-05-01)

参考文献数

110

被引用文献数

2

---

Vaccines have contributed to the prevention of infectious diseases for a long time. Pathogen-derived antigens and adjuvants in vaccine formulations stimulate immune cells to elicit humoral and cellular immune responses against pathogens. Achieving highly immune responses with decreased adverse effects requires the development of a system that can deliver antigens to specific immune cells. Dendritic cells (DCs) are well-known professional antigen presenting cells (APCs) that initiate acquired immune responses by presenting antigens to T cells. Accordingly, DC-targeted vaccines have been investigated and applied in clinical trials for the treatment of infectious diseases and for chronic diseases such as cancers. In addition to DCs, B lymphocytes are regarded as professional APCs despite their primary role in humoral immunity. Therefore, B cell-targeted vaccines are also expected to elicit both humoral and cellular immune responses. In this review we summarize the basic functions of DCs and B cells as APCs. We also provide information on DC and B cell targeted vaccines in preclinical and clinical settings. Finally, we introduce our novel antigen delivery system that targets splenic marginal zone B cells and the ability of this system to act as a novel vaccine that elicits both humoral and cellular immune responses.

著者

Shabana Iqrar Khan Ehab Ahmed Abourashed Ikhlas Ahmad Khan Larry Anthony Walker

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.52, no.4, pp.394-397, 2004 (Released:2004-04-01)

参考文献数

23

被引用文献数

19 21

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This study examined the intestinal transport of five harman alkaloids using the Caco-2 cell monolayer as a model of the human intestinal mucosa. Transport parameters, permeability coefficients and percent transports, were calculated and compared under identical conditions with atenolol. Permeability coefficients were also compared with the reported values for model compounds like mannitol, propranolol and glucose. Sodium fluorescein was used as the marker for paracellular leakage. These alkaloids, in the concentration range of 250—500 μM, demonstrated substantial transport across the monolayer with moderate to high efflux rates and permeability coefficients. The transport was linear with time and was concentration dependent.

著者

Yoshimitsu Yamazaki Yasuhiro Kawano

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.59, no.3, pp.388-391, 2011-03-01 (Released:2011-03-01)

参考文献数

29

被引用文献数

32 43

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It is beneficial to treat chronic inflammatory condition in patients through diets that inhibit the production of proinflammatory cytokines and mediators such as tumor necrosis factor-α (TNF-α) and nitric oxide (NO). Since less attention has been paid to alkaloids in the diets than to polyphenols in this regard, we aimed at investigating anti-inflammatory activity of herb-derived alkaloids through suppression of TNF-α and NO production in lipopolysaccharide (LPS)-stimulated mouse RAW264 and/or human THP-1 cells. A harmala alkaloid, harmine, an opium alkaloid, papaverine, and Lycoris alkaloids, lycorine and lycoricidinol, showed TNF-α suppressive activities stronger than or comparable to that of a reference polyphenol, butein, in RAW264 cells (IC50=4, 10, 2.1, 0.02, and 8 μM, respectively). Other alkaloids showed no or marginal to moderate inhibitory activities. Similar tendency of inhibition was found for NO production in RAW264 cells and TNF-α production in THP-1 cells. In addition, harmine was found to suppress interleukin-6 (IL-6) production in RAW264 cells. The above four inhibitory alkaloids had essentially no antioxidative property in the superoxide anion scavenging assay. Western blotting and reverse transcriptase-polymerase chain reaction (RT-PCR) showed that harmine caused neither prevention of nuclear factor-κB (NF-κB) translocation into the nucleus nor inhibition of p38 mitogen activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) phosphorylation, while that the LPS-induced transcription of TNF-α and inducible NO synthase was dose-dependently attenuated by harmine. This result suggests that the molecular mechanism of harmine action is different from those of many other anti-inflammatory phytochemicals. In conclusion, some herbal alkaloids like harmine, in spite of lacking antioxidative property, have potential as anti-inflammatory agents that strongly suppress TNF-α and NO production by a unique mechanism.

著者

Kazuma Shioe Shingo Ishikura Yoshikazu Horino Hitoshi Abe

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.61, no.12, pp.1308-1314, 2013-12-01 (Released:2013-12-01)

参考文献数

32

被引用文献数

11 13

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A facile method for the synthesis of dehydrodigallic acid, which is a fundamental structure of ellagitannins, was developed. A classical Ullmann condition was effective for the formation of the highly hindered biaryl ether structure, and we clarified that the suitable protection of the phenolic hydroxy groups was crucial in this reaction. In this way, the synthesis of dehydrodigallic acid and its derivative was successfully performed. The described method would provide a synthetic utility toward ellagitannins.

著者

Hirotaka Sasa Koyo Mori Kotaro Kikushima Yasuyuki Kita Toshifumi Dohi

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.2, pp.106-110, 2022-02-01 (Released:2022-02-01)

参考文献数

48

被引用文献数

8

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Benzolactams have unique biological activity and high utility in the synthesis of valuable compounds with direct applicability to oxindole alkaloids and antibacterial agents. Despite recent advances in organic chemistry and the growing number of reported methods for synthesizing benzolactams, their preparation still requires a multistep process. C–H amination reactions can convert aromatic C(sp2)–H bonds directly to C(sp2)–N bonds, and this direct approach to C–N bond formation offers effective access to benzolactams. Hypervalent iodine reagents are promising tools for achieving oxidative C–H amination. Motivated by our ongoing research efforts toward the development of useful hypervalent-iodine-mediated oxidative transformations, we herein describe an effective intramolecular oxidative C–H amination reaction based on μ-oxo hypervalent iodine catalysis for the synthesis of benzolactams bearing various functional groups.

著者

Hirohito Ikeda Masatomo Yamanaka Shota Takahashi Tomonori Ohata Miho Yukawa Rie Nakashima Hiroyuki Tsutsumi Masao Fujisawa Hatsumi Aki

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.3, pp.230-234, 2022-03-01 (Released:2022-03-01)

参考文献数

26

被引用文献数

2

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The details of incompatibility between aripiprazole (ARIP) oral solution and green tea were examined. When the ARIP oral solution was mixed with a commercial PET bottled green tea beverage, the residual rate of ARIP in the mixed solution decreased to 15.7–17.6%. Mixing with ARIP reduced the content of gallate-type green tea polyphenols (GTPs) in the mixed solution but not the content of non-gallate-type GTPs. Furthermore, using pH 3.0 lactic acid buffer, 2.23 mM ARIP solution and 2.23 mM GTP solution were prepared, and the same volumes of ARIP solution and GTP solution were mixed. When the gallate-type GTP solution was mixed, the residual rate of ARIP in the mixed solution decreased. On the other hand, when the non-gallate-type GTP solution was mixed, the residual rate of ARIP in the mixed solution did not decrease. From the above results, it was found that the main reason for the incompatibility between ARIP oral solution and green tea was the formation of an insoluble substance composed of ARIP and gallate-type GTPs in green tea. Furthermore, experimental results using the continuous variation method revealed that ARIP and (−)-epigallocatechin gallate, which is the most representative gallate-type GTP, interact at a molar ratio of 3 : 2.

著者

Shoji Maehara Manami Kobayashi Mari Kuwada Tominari Choshi Hirofumi Inoue Yuhzou Hieda Takashi Nishiyama Toshiyuki Hata

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.70, no.3, pp.195-198, 2022-03-01 (Released:2022-03-01)

参考文献数

17

被引用文献数

4

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We investigated similar compounds to ebselen and tideglusib, which exhibit strong activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using Molecular ACCess System (MACCS) keys. Four candidate compounds were identified. One of them, phenyl-benzothiazol-3-one, showed coronavirus-specific 3C-like (3CL) protease inhibitory activity. The results indicated that a similarity score above 0.81 is a good indicator of activity for ebselen-and-tideglusib-like compounds. Subsequently, we simulated the ring-cleavage Michael reaction of ebselen at the Se center, which is responsible for its 3CL protease inhibitory activity, and determined the activation free energy of the reaction. The results showed that reaction simulation is a useful tool for estimating the activity of inhibitory compounds that undergo Michael addition reactions with the relevant cysteine S atom of 3CL proteases.

著者

SHOICHIRO OZAKI TOSHIO NAGASE HIROFUMI TAMAI HARUKI MORI AKIO HOSHI MASAAKI IIGO

出版者

The Pharmaceutical Society of Japan

雑誌

Chemical and Pharmaceutical Bulletin (ISSN:00092363)

巻号頁・発行日

vol.35, no.9, pp.3894-3897, 1987-09-25 (Released:2009-10-19)

参考文献数

11

被引用文献数

8 9

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For the purpose of diminishing the toxicity of 5-fluorouracil (1) and obtaining biologically active derivatives of 1 suitable for oral administration, alkylthiomethyl, alkylsulfinylmethyl, alkylsulfonylmethyl, and acylthiomethyl groups were introduced at the 1- and 3-positions of 1. The antitumor activity of these synthetic compounds was tested against L1210 leukemia in mice. 1-Alkylthiomethyl-5-fluorouracils showed weak antitumor activity at a high dose (300 mg/kg).