著者

芳生 秀光

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.130, no.9, pp.1143-1156, 2010 (Released:2010-09-01)

参考文献数

77

被引用文献数

2 5

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Mercury and its organic compounds, especially methylmercury are extremely hazardous pollutants that have been released into the environment in substantial quantities by natural events and anthropogenic activities. Due to the acute toxicity of these contaminants, there is an urgent need to develop an effective and affordable technology to remove them from the environments. Recently, attempts have been made to utilize bacterial mer operon-mediated reduction and volatilization of mercurials for environmental remediation of mercury pollution. However, application of this technology to the treatment of mercury-contaminated environments has been limited by social concerns about the release of volatile mercury that will become part of the local mercury cycle and repollute the environment again, into the ambient air. To improve this environmental problem, a new mercury scavenging mechanism that could be expressed in living cells and accumulates mercury from contaminated site without releasing mercury vapor is necessitated. To construct a new biocatalyst that is capable of specifically accumulating mercury from contaminated sites without releasing mercury vapor, we have genetically engineered bacteria and tobacco plant for removal of mercury from wastewater and soils, respectively, to express a mercury transport system and organomercurial lyase enzyme simultaneously, and overexpress polyphosphate, a chelator of divalent metals. The applicability of these new engineered biocatalysts in the environmental remediation of mercurials is evaluated and discussed in this review.

著者

冨田 隆志

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.137, no.12, pp.1497-1504, 2017 (Released:2017-12-01)

参考文献数

31

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Several issues concerning medicines remain unclear, including the availability of known, but not easily recognizable information. This review evaluates the mechanisms of side effects and the various risk indications included in package inserts. The results can be summarized as follows. 1) Short-term exposure to gatifloxacin significantly induced insulin secretion and increased the cytosolic Ca2+ concentration of islet cells by augmenting extracellular Ca2+ influx and its release from the endoplasmic reticulum. Alternatively, there was a decline in the cellular insulin level and reactivity to sulfonylurea after prolonged exposure. The insulin depletion was greater than that produced by other fluoroquinolones. 2) The elution of di(2-ethylhexyl)phthalate (DEHP) from the infusion set could be associated with the solubilizers in the injection medicines. The package inserts of several products containing polysorbate or ethanol had no warning about DEHP. Although there was a slight correlation between polysorbate content and descriptions on package inserts, the use of DEHP-containing devices was prohibited for some products, even with limited amounts of polysorbate. Therefore, the package insert statements should be reviewed to reflect appropriately the extent of DEHP elution. 3) Risk management plan consists of strategies to minimize the potential risks of medicines. One approach could be to introduce reminders on package inserts; however, of 268 potential risks associated with 81 products, 56 were not mentioned in package inserts. Because most postmarketing pharmacovigilance plans depend on spontaneous reporting by healthcare personnel, the descriptions on package inserts should be reexamined.

著者

吉永 智一

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.53, no.6, pp.565-569, 2017 (Released:2017-06-01)

参考文献数

15

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エイズはHIVが感染することにより引き起こされる疾患であり、未だ世界的に深刻な感染症である。我々はインテグラーゼ阻害剤として世界で最初に臨床試験に進んだS-1360を創製したが、ヒトでの代謝が早く、薬効を確認できなかった。しかし、その過程で学びがあり、特に、「2メタル結合ファーマコフォアモデル」を見出し、多種多様な化合物をデザインし、GSKとの共同研究の中でドルテグラビルを創製した。本稿では、ドルテグラビル創製までの苦難の道のりを振り返りたい。

著者

吉永 智一

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.53, no.6, pp.565-569, 2017

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エイズはHIVが感染することにより引き起こされる疾患であり、未だ世界的に深刻な感染症である。我々はインテグラーゼ阻害剤として世界で最初に臨床試験に進んだS-1360を創製したが、ヒトでの代謝が早く、薬効を確認できなかった。しかし、その過程で学びがあり、特に、「2メタル結合ファーマコフォアモデル」を見出し、多種多様な化合物をデザインし、GSKとの共同研究の中でドルテグラビルを創製した。本稿では、ドルテグラビル創製までの苦難の道のりを振り返りたい。

著者

伴 義雄

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.25, no.2, 1989

著者

今野 博行

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.50, no.5, pp.452-452, 2014

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天然物由来の医薬品リード化合物が枯渇していると言われて久しい.重要な標的の1つであるケモカインレセプター阻害剤に限ると,天然物由来阻害剤は海綿由来異常アミノ酸含有デプシペプチド(エステル結合を持つぺプチド)類,アニバミン類のみではないだろうか.しかし,その阻害能は強力であり,これらの全合成,構造活性相関研究は,いまだ魅力的である.なお,本稿は下記の文献に基づいて,その研究成果を紹介するものである.1) Pelay-Gimeno M. et al., Marine drugs., 11, 1693-1717 (2013).2) Zhang F. et al., J. Org. Chem., 76, 7945-7952 (2011).3) Albericio F. et al., Nature Commun., 4, 2352 (2013).4) Coellp L. et al., Int. Appl. Pat., WO2010/070078A1 (2010).

著者

石塚 秀夫 新間 信夫 堀井 郁夫

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.119, no.12, pp.881-897, 1999-12-01 (Released:2008-05-30)

参考文献数

49

被引用文献数

14 19

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Capecitabine (N4-pentyloxycarbonyl-5'-deoxy-5-fluorocytidine) is a novel oral fluoropyrimidine carbamate, which was designed to be sequentially converted to 5-fluorouracil (5-FU) by three enzymes located in the liver and in tumors. N4-alkoxycarbonyl-5'-deoxy-5-fluorocytidine derivatives including capecitabine pass intact through the intestinal tract and are sequentially converted to 5-FU by a cascade of the three anzymes. The first step is the conversion to 5'-deoxy-5-fluorocytidine (5'-DFCR) by carboxylesterase located in the liver, then to 5'-deoxy-5-fluorouridine (5'-DFUR) by cytidine deaminase highly expressed in the liver and various solid tumors, and finally to 5-FU by thymidine phosphorylase (dThdPase) preferentially located in tumor tissues. Among large numbers of the derivatives, capecitabine was selected based on its susceptibility to hepatic carboxylesterase, oral bioavailability in monkeys and efficacy in a human cancer xenograft. Capecitabine given orally yielded substantially higher concentrations of 5-FU within tumors than in plasma or normal tissue (muscle). The tumor 5-FU levels were also much higher than those achieved by intraperitoneal administration of 5-FU at equi-toxic doses. This tumor selective delivery of 5-FU ensured greater efficacy and a more favourable safety profile than with other fluoropyrimidines. In 24 human cancer xenograft models studied, capecitabine was more effective at a wider dose range and had a broader spectrum of antitumor activity than 5-FU, UFT or its intermediate metabolite 5'-DFUR. The susceptibility of the xenografts to capecitabine correlated with tumor dThdPase levels. Moreover, the conversion of 5'-DFUR to 5-FU by dThdPase in tumor was insufficient in a xenograft model refractory to capecitabine. In addition, the efficacy of capecitabine was enhanced by dThdPase up-regulators, such as by taxanes and cyclophosphamide and by X-ray irradiation. The efficacy of capecitabine may, therefore, be optimized by selecting the most appropriate patient population based on dThdPase status and/or by combining it with dThdPase up-regulators. Capecitabine has additional characteristics not found with 5-FU, such as potent antimetastatic and anticachectic actions in mouse tumor models. With these profiles, capecitabine may have substantial potential in cancer treatment.

著者

Zhang Bingyu Lv Chao Li Weibo Cui Zhiming Chen Dongdong Cao Fangjun Miao Fang Zhou Le

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

2015

被引用文献数

17

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This 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.

著者

橋本 寿夫

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア

巻号頁・発行日

vol.52, no.9, pp.837-839, 2016

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鹿沼市は麻の生産量日本一の産地。優れた品質の「野州麻」を古くから全国各地に出荷してきた。しかし代替繊維の台頭などにより栽培面積は激減。幻覚成分が含まれる麻の盗難も相次ぎ野州麻が存続の危機に。そうした中、栃木県農業試験場が無毒麻「とちぎしろ」の生育に成功。現在も無毒性維持のための栽培を続けている。<br>後継者不足から産地としての存続が危ぶまれているが、最近、麻の栽培技術継承の動きや付加価値を付けての商品化などの取り組みも生まれてきている。

著者

高柳 弘明 後藤 元彰 武田 收功 長 由美子

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.124, no.11, pp.751-767, 2004 (Released:2004-11-01)

参考文献数

23

被引用文献数

6 11

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Picric acid forms stable picrates with various organic molecules through π- bonding or ionic bonding, and such picrates have been very useful for identification and qualitative analysis. As it seemed desirable to determine the crystal structures and the bonding mode of picrates of basic organic compounds, we have investigated the crystal structures of aromatic hydrocarbons, aromatic amino compounds, heterocyclic compounds and so on. A series of our studies on the crystal structure of basic organic compounds have shown that the complexes of picric acid and aromatic hydrocarbons are formed through π-bonding, and those of aromatic heterocyclic compounds are formed through ionic and hydrogen bonding; in addition, some of them also have π-bonding.

著者

川西 徹

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.48, no.2, pp.119-123, 2012-02-01 (Released:2016-12-16)

出版者

公益社団法人 日本薬学会

雑誌

藥學雜誌 (ISSN:00316903)

巻号頁・発行日

vol.51, no.4, pp.302-335, 1931-04-26 (Released:2009-11-13)

著者

笠松 真吾 守田 匡伸 赤池 孝章

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.53, no.3, pp.210-214, 2017 (Released:2017-03-01)

参考文献数

23

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活性酸素種(ROS)は、非特異的化学修飾をもたらす毒性因子としての側面の他に、生理的な細胞内シグナル(レドックスシグナル)分子としての機能を持つ。ROS・レドックスシグナルはその下流で生じる親電子物質を介して巧妙に制御されている。最近、新規レドックスシグナル制御因子として活性イオウ分子種が同定された。活性イオウ分子種によるレドックスシグナル制御機構の解析は、酸化ストレスの関わる疾病の新規予防・治療戦略の開発に寄与すると期待される。

著者

高木 敏之 木本 茂 牧野 由紀子 那須 正夫

出版者

公益社団法人 日本薬学会

雑誌

衛生化学 (ISSN:0013273X)

巻号頁・発行日

vol.43, no.3, pp.197-201, 1997-06-30 (Released:2008-05-30)

参考文献数

2

被引用文献数

3 2

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The recently abused substances called "legal drugs", such as Natural Ecstacy, Herbal Ecstacy and RUSH, were analyzed to confirm that they contain no controlled drugs using gas chromatography (GC) and gas chromatography-mass spectrometry (GC-MS). Seventeen samples were examined for narcotics, stimulants or other controlled substances. While none of them were detected, ephedrine and pseudoephedrine were found in five samples. Their concentrations were determined by high-performance liquid chromatography (LC) to be below ten per cent, within the limit regulated by the stimulants control law. Caffeine was also detected in seven samples. Therefore, the exciting effect of the "legal drugs" was considered to be caused by ephedrine, pseudoephedrine and caffeine.

著者

東田 道久

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.47, no.7, pp.612-612, 2011-07-01 (Released:2017-04-18)

著者

才川 勇 桃井 海秀 酒井 広志 高下 寛 大橋 俊則 南 尚 山本 芳子 福岡 義和

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.99, no.12, pp.1207-1218, 1979-12-25 (Released:2008-05-30)

参考文献数

16

被引用文献数

3 3

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The stability, degradation pattern and structure of degradation products of sodium 7-[D (-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamido]-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate (T-1551) in aqueous solution were investigated. T-1551 was kept in various solutions in pH and μ=0.5 at 35°, its degradation was followed by HPLC. T-1551 was stable at the range of pH 4.0-7.0, slightly unstable at acid and markedly unstable at alkaline. It was confirmed that in alkaline solution, 7-[D (-)-α-[3-[2-(N-ethyl-N-oxaloamino)-ethyl] ureido]-α-(4-hydroxyphenyl) acetamido]-3-(1-methyl-1H-tetrazol-5-yl) thiomethyl-3-cephem-4-carboxylic acid (T-1551A) was produced, and that in acidic solution, 7-[D (-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamido]-3-hydroxy-methyl-3-cephem-4-carboxylic acid γ-lactone (T-1551B), 7-[D (-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamido]-3-hydroxymethyl-3-cephem-4-carboxylic acid (T-1551C), 5-mercapto-1-methyl-1H-tetrazole (T-1551F), 2-[2-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-2-(4-hydroxyphenyl) acetamido]-2-[1, 2, 5, 7-tetrahydro-7-oxo-4H-furo [3, 4-d] [1, 3] thiazin-2-yl] acetic acid (T-1551G), 2-[α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamidomethyl]-2, 3-dihydro-5-hydroxy-methyl-6H-thiazine-4-carboxylic acid γ-lactone (T-1551H) and N-formylmethyl-D-(-)-α-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-α-(4-hydroxyphenyl) acetamide (T-1551D) were produced, respectively.

著者

山本 佳久

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.49, no.4, pp.340-340, 2013-04-01 (Released:2016-09-26)

著者

野村 渉

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.137, no.10, pp.1223-1231, 2017 (Released:2017-10-01)

参考文献数

17

被引用文献数

1

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Interactions between bio-macromolecules such as proteins, DNA, and polysaccharides play pivotal roles in maintaining homeostasis in living systems. For elucidating the function of biomolecules, peptides are powerful tools, compared to native proteins, because of their lower molecular weights, compatibility with chemical modification, and predictability of interaction with the target molecules. These advantages enabled us to develop peptide-based functional molecules. However, for the purposes of controlling or regulating biomolecule functions, designing artificial proteins is also an effective approach. Not only rational protein design, but also directed molecular evolution, are now regarded as powerful methods for optimizing protein function. The interactions of proteins with bio-macromolecules are usually highly specific and show high affinity because of larger interaction surfaces as compared to small molecules or peptides. Thus, the use of proteins for designing biofunctional molecules is also important for wider applications in the biotechnology field. In this review, four topics will be discussed: 1) the development of fluorescently-labeled ligands for G protein-coupled receptors (GPCR), as well as bivalent ligands for GPCR imaging and function analysis, 2) the design and synthesis of gp41 trimer mimics as HIV-1 inhibitors or vaccines, 3) the development of a ZIP tag-probe system and its application to intracellular protein imaging, and 4) the functional analysis of sequence-specific DNA recombinase for expanding the scope of genome editing. The results of these studies indicate the importance of precision in the design of peptides or proteins for regulating bio-macromolecular interactions.

著者

湯本 史明

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.50, no.5, pp.442_3-442_3, 2014 (Released:2016-06-21)

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生体分子を急速に凍結させ,低温に保ったまま電子顕微鏡で解析する手法のことである.染色や固定をするわけではないことから,生体分子をそのまま観察することが可能となる.ここ最近は,検出量子効率の高い検出器やソフトウェアの開発をはじめとした解析技術の発展が相まって,比較的短期間に高分解能で単粒子構造解析を行った例が次々に報告されてきている.

著者

亀谷 哲治 高野 誠一 寺沢 弘文 武田 裕光

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.92, no.7, pp.868-870, 1972-07-25 (Released:2008-05-30)

参考文献数

6

被引用文献数

3 4

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In order to obtain 2, 6-dicyano-7-ethoxycarbonyl-1, 5-dioxo-1, 2, 3, 5-tetrahydroindolizine as an intermediate for the synthesis of camptothecin, Michael condensation of methyl 3-cyano-4-ethoxycarbonyl-1, 2-dihydro-2-oxopyridine-6-carboxylate (V) with acrylonitrile was carried out but failed to afford the objective substance. A similar condensation of V with t-butyl acrylate also resulted in failure. Ethyl 5-cyano-4-ethoxycarbonyl-5-oxo1, 6-dihydro-2-pyridine glyoxylate (VIII) was synthesized by the reaction of 3-cyano-4-ethoxycarbonyl-1, 2-dihydro-2-oxopyridine-6-carboxylic acid chloride with ethyl t-butylmalonate. Although cyclization of VIII to ethyl 6-cyano-1, 2, 3, 5-tetrahydro-1, 3, 5-trioxo-7-indolizine carboxylate (IX) was unsuccessful, Friedlander reaction of VIII with 2-aminobenzaldehyde gave the expected 8-cyano-7-ethoxycarbonyl-9, 11-dihydro-9, 11-dioxoindolizino[1, 2-b]quinoline (X) in one step.