著者

川田 十三夫 佐藤 成美 山下 彦王 宅見 賢二 采見 憲男 渡辺 健二

出版者

公益社団法人 日本食品衛生学会

雑誌

食品衛生学雑誌 (ISSN:00156426)

巻号頁・発行日

vol.9, no.5, pp.358-363, 1968

被引用文献数

1

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Cells of <I>Clostridium botulinum</I> type A strain 190 grown in thioglycolate medium (GYPT medium) autolysed after having reached a maximum growth. This strain was dissociated into large and small colony-forming types in semisolid media. The cells obtained from the large colony type autolysed more rapidly than those from small one. Washed cells harvested at logarithmic growth phase lysed in phosphate buffer at 37&deg;C within 2-3 hours. Autolysis rose above pH 6.0 and was optimal near pH 7.0. The potential for autolysis reached a maximum toward the end of the logarithmic growth phase and thereafter the cells became resistant to autolysis. The autolytic activity was destreyed by heating the cells at 60&deg;C for 10 minutes and was slightly affected by cysteine (10<SUP>-2</SUP>M), N-ethylmaleimide (10<SUP>-2</SUP>M) and mercaptoethanol (10<SUP>-1</SUP>M).<BR>During autolysis nitrogen, protein, nucleic acids, reducing sugars, amino sugars and botulinum toxin were released from the cells as the reduction of the turbidity in cell suspension occurred. Electron microscopic observations on the process of autolysis revealed that the partial lysis of walls occurred first at the end of the organism and the cytoplasmic contents were lost through such lesions. The lysis of the wall centripetally spread and finally the morphological entity of the wall was completely lost. From these findings it is suggested that the autolysis may be proceded by auto-digestion of the cell wall at the end of the organism.

著者

山下 純一 山脇 一郎 上田 修一 安本 三治 采見 憲男 橋本 貞夫

出版者

公益社団法人日本薬学会

雑誌

Chemical & pharmaceutical bulletin (ISSN:00092363)

巻号頁・発行日

vol.30, no.12, pp.4258-4267, 1982-12-25

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Six types of 5-fluorouracil (5-FU) derivatives were synthesized ; namely, 2,4-di-O-substituted, 2-O-substituted, 4-O-substituted, 1,3-disubstituted, 1-substituted and 3-substituted compounds. After oral administration of these compounds to rats, the blood levels of 5-FU were determined. Among O-substituted derivatives, a 4-O-substituted derivative was most easily activated to 5-FU and 2-O-substituted derivatives were next most easily activated. Among N-substituted derivatives, acyl and sulfonyl derivatives showed the highest 5-FU releasing abilities and 1-alkoxymethyl substituted derivatives showed low ability. N-Alkyl substituted derivatives were not activated to 5-FU. Several compounds which gave higher blood levels of 5-FU than that obtained with 1-(tetrahydro-2-furyl)-5-fluorouracil (Thf-FU), as well as same related compounds, were selected and their antitumor activities were examined. The 2-O-substituted derivatives, 2-butoxy-5-fluoro-4 (1H)-pyrimidone (11) and 2-benzyloxy-5-fluoro-4 (1H)-pyrimidone (19), were as effective as Thf-FU. The activities of 2,4-di-O-substituted derivatives, 2,4-dibutoxy-5-fluoropyrimidine (1) and 2,4-dibenzyloxy-5-fluoropyrimidine (6), against Ehrlich carcinoma and against sarcoma 180,respectively, were the same as those of Thf-FU. The 1-substituted derivatives, 1-ethoxymethyl-5-fluorouracil (49) and 1-(1-ethoxy-1-phenylmethyl)-5-fluorouracil (50), were found to be as effective as Thf-FU.

著者

山下 純一 武田 節夫 松本 宏 寺田 忠史 采見 憲男 安本 三治

出版者

公益社団法人日本薬学会

雑誌

Chemical & pharmaceutical bulletin (ISSN:00092363)

巻号頁・発行日

vol.35, no.5, pp.2090-2094, 1987-05-25

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Various O-acyl and N-acyl derivatives of 2'-deoxy-5-trifluoromethyluridine (F_3Thd) were synthesized; namely 5'-O-acyl, 3',5'-di-O-acyl, N^3-acyl, 3',5'-di-O-acetyl-N^3-acyl, 3',5'-di-O-carbamoyl and 3',5'-di-O-ethoxycarbonyl compounds. 5'-O-Acyl derivatives of 2'-deoxy-5-trifluoromethylcytidine were also synthesized. The antitumor activities of these compounds against sarcoma 180 were examined by oral administration to mice. Among the 5'- and 3',5'-diester compounds with aliphatic acids, the 5'-O-hexanoyl compound showed the highest activity. Full protection of the sugar moiety with aroyl or carbamoyl groups considerably decreased the activities, and those of the 3',5'-di-O-m-fluorobenzoyl and 3',5'-di-O-butylcarbamoyl compounds were the smallest. N^3-Benzoyl compounds were slightly more effective than F_3Thd but none of them showed higher activity than the effective O-acyl compounds. In the case of 5'-O-acylates of 2'-deoxy-5-trifluoroniethylcytidine, the 5'-O-benzoyl compound showed the highest activity.

著者

山下 純一 武田 節夫 松本 宏 采見 憲男 安本 三治

出版者

公益社団法人日本薬学会

雑誌

Chem. Pharm. Bull. (ISSN:00092363)

巻号頁・発行日

vol.35, pp.2373-2381, 1987

被引用文献数

1

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Various O-alkoxyalkyl derivatives of 2'-deoxy-5-trifluoroniethyluridine(F_3Thd) were synthesized, and the antitumor activities of the compounds against sarcoma 180 were examined by oral administration to mice. Among the formal-type derivatives, 3',5'-di-O-ethoxymethyl (3), 3',5'-di-O-benzyloxyinethyl (12), 5'-O-benzyloxymethyl (13) and 3'-O-benzyloxymethyl (14) compounds showed high activities, which were six-fold higher than that of F_3Thd itself. Since acetal-type derivatives were unstable under acidic conditions, antitumor testing of the compounds was also carried out with co-administration of sodium bicarbonate. 5 '-O-(1-Ethoxypropyl)-F_3Thd (25) and 5'-O-(1-benz:yloxypropyl)-F_3Thd (37) showed the highest activities among the acetal-type derivatives, but the ED_50 values of the compounds were not lower than those of effective formal-type compounds. These O-alkoxyalkyl derivatives of F_3Thd are resistant to degradation by thymidine phosphorylase and are activated by microsornal drug-metabolizing enzymes after absorption.

著者

山下 純一 山脇 一郎 上田 修一 安本 三治 采見 憲男 橋本 貞夫

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.12, pp.4258-4267, 1982-12-25 (Released:2008-03-31)

参考文献数

32

被引用文献数

15 18

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Six types of 5-fluorouracil (5-FU) derivatives were synthesized ; namely, 2, 4-di-O-substituted, 2-O-substituted, 4-O-substituted, 1, 3-disubstituted, 1-substituted and 3-substituted compounds. After oral administration of these compounds to rats, the blood levels of 5-FU were determined. Among O-substituted derivatives, a 4-O-substituted derivative was most easily activated to 5-FU and 2-O-substituted derivatives were next most easily activated. Among N-substituted derivatives, acyl and sulfonyl derivatives showed the highest 5-FU releasing abilities and 1-alkoxymethyl substituted derivatives showed low ability. N-Alkyl substituted derivatives were not activated to 5-FU. Several compounds which gave higher blood levels of 5-FU than that obtained with 1-(tetrahydro-2-furyl)-5-fluorouracil (Thf-FU), as well as same related compounds, were selected and their antitumor activities were examined. The 2-O-substituted derivatives, 2-butoxy-5-fluoro-4 (1H)-pyrimidone (11) and 2-benzyloxy-5-fluoro-4 (1H)-pyrimidone (19), were as effective as Thf-FU. The activities of 2, 4-di-O-substituted derivatives, 2, 4-dibutoxy-5-fluoropyrimidine (1) and 2, 4-dibenzyloxy-5-fluoropyrimidine (6), against Ehrlich carcinoma and against sarcoma 180, respectively, were the same as those of Thf-FU. The 1-substituted derivatives, 1-ethoxymethyl-5-fluorouracil (49) and 1-(1-ethoxy-1-phenylmethyl)-5-fluorouracil (50), were found to be as effective as Thf-FU.

著者

采見 憲男 武田 節夫 北里 健二 梶原 大義 藤井 節郎

出版者

公益社団法人 日本化学療法学会

雑誌

CHEMOTHERAPY (ISSN:00093165)

巻号頁・発行日

vol.26, no.2, pp.200-208, 1978-03-25 (Released:2011-03-08)

参考文献数

13

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The antitumor activity of 1, 3-Bis (tetrahydro-2-furanyl) -5-fluoro-2, 4-pyrimidinedione (FD-1) was compared with that of 1- (2-Tetrahydrofuryl) -5-fluorouracil (FT) or 5-Fluorouracil (5-FU) in a number of tumor systems.FD-1 had significant activity against the solid forms but not the ascitic forms, and it produced a greater inhibition in tumor growth than FT. On AH 130 solid form, the therapeutic index (LD50/ED50) of FD-1 and FT were respectively 18. 3 and 10.6.FD-1 was evaluated against the ip and sc implanted L 1210 leukemia by single, intermittent or daily administration. FD-1 retained some degree of antileukemic activity against the ic implanted L 1210.No significant difference in antitumor activity was observed between the R and S isomers or the racemic mixture (FD-1).A higher activity of FD-1 compared to FT was possibly due to the increased 5-FU level in tumor through its metabolite, 3- (tetrahydro-2-furanyl) -5-fluoro-2, 4-pyrimidinedione (3-FT).

著者

采見 憲男

出版者

篠原出版新社

雑誌

癌の臨床 (ISSN:00214949)

巻号頁・発行日

vol.17, no.10, pp.731-742, 1971-10

著者

戸出 英輝 采見 憲男 川口 安郎 多比良 和基

出版者

公益社団法人 日本化学療法学会

雑誌

CHEMOTHERAPY (ISSN:00093165)

巻号頁・発行日

vol.25, no.2, pp.385-391, 1977-02-25 (Released:2011-03-08)

参考文献数

11

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FT-207 was activated to 5-FU by microsomal drug-metabolizing enzyme in the liver, and 5-FU was converted to F-β-alanine etc. in the microsomal supernatants or to FuR etc. in the nucleus.After administration of FT-207, 5-FU activated in the liver was released into the blood and then transferred to the tumor tissues.On the other hand, in experiment of the rat treated with CCl4 in vivo and of the activation of FT-207 by several tissues in vivo, it was observed that FT-207 was activated in the lung, the kidney and spontaneously besides the liver.After administration of 3H-FT-207, the radioactivities were incorporated as FUMP into the RNA fraction of tumor cells.Based on these results, we postulated that FT-207 was activated to 5-FU mainly in the liver, partially in the lung, the kidney enzymatically and in whole bodies spontaneously, was transferred to the tumor tissues and remarkably inhibited the RNA and DNA synthesis.

著者

藤井 節郎 中村 芳正 武田 節夫 森田 健一 佐藤 俊幸 丸中 照義 川口 安郎 采見 憲男

出版者

The Japanese Cancer Association

雑誌

GANN Japanese Journal of Cancer Research (ISSN:0016450X)

巻号頁・発行日

vol.71, no.1, pp.30-44, 1980-02-29 (Released:2008-10-23)

参考文献数

14

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The metabolism, antitumor activity, and acute toxicity of 5-fluoro-1, 3-bis-(tetrahydro-2-furanyl)-2, 4-pyrimidinedione (FD-1) were investigated in animals, compared with 5-fluoro-1-(tetrahydro-2-furanyl)-2, 4-pyrimidinedione (FT). It was found that after oral administration of FD-1, the level of 5-fluorouracil (5-FU) was maintained higher and longer than after administration of FT, and that a large amount of 5-FU was released from FD-1 by liver microsomal drugmetabolizing enzymes or spontaneous hydrolysis via 5-fluoro-3-(tetrahydro-2-furanyl)-2, 4-pyrimidinedione (3-FT) and FT. FD-1 had a significant activity against the solid form of Ehrlich carcinoma, sarcoma-180, hepatoma AH130, Yoshida sarcoma, Walker carcinosarcoma-256, and leukemia L1210 and P388, but not the ascitic forms, and it produced greater inhibition of tumor growth than FT. The acute toxicity of FD-1 was less than that of FT.

著者

安田 行寛 東郷 常夫 采見 憲男 渡辺 昭治 播磨 耕介 鈴江 崇志

出版者

公益社団法人 日本化学療法学会

雑誌

CHEMOTHERAPY (ISSN:00093165)

巻号頁・発行日

vol.21, no.6, pp.1171-1178, 1973-08-25 (Released:2011-03-08)

参考文献数

9

被引用文献数

1

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N1-(2-Tetrahydrofuryl)-5-fluorouracil (FT-207), a new antimetabolic anticancer agent synthesized in USSR, was studied on antimicrobial activity in vitro and distribution, excretion and metabolism in vivo.The results obtained were as follows.1) Antimicrobial activityFT-207 showed fairly active against Micrococcus flavus ATCC 10240, Sarcina lutea PCI 1001, Staphylococcus epidermidis and Staphylococcus aureus 209 P, but in general the activity was inferior to that of 5-FU.2) DistributionBy the intravenous administration of FT-207, 400mg/kg, in normal and AH-130 bearing rats, the concentration of FT-207 in serum and tissues maintained measurably until 16-24 hours.On the other hand, the active substances (5-FU, etc.) from FT-207 detected at 1-4 hours and peaked at 4-16 hours in tissues.3) Urinary excretionFT-207 and its active substances were excreted in urine for a long time, and the recoveries of FT-207 for 48 hours in rats, mice and rabbits were 12-18%.4) MetabolismIn normal and AH-130 bearing rats, the main active substance from FT-207 administrated intravenously was 5-FU.

著者

安田 行寛 東郷 常夫 采見 憲男 渡辺 昭治 播磨 耕介 鈴江 崇志

出版者

公益社団法人 日本化学療法学会

雑誌

日本化学療法学会雑誌 (ISSN:00093165)

巻号頁・発行日

vol.21, no.6, pp.1171-1178, 1973

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N<SUB>1</SUB>-(2-Tetrahydrofuryl)-5-fluorouracil (FT-207), a new antimetabolic anticancer agent synthesized in USSR, was studied on antimicrobial activity <I>in vitro</I> and distribution, excretion and metabolism <I>in vivo</I>.<BR>The results obtained were as follows.<BR>1) Antimicrobial activity<BR>FT-207 showed fairly active against <I>Micrococcus flavus</I> ATCC 10240, <I>Sarcina lutea</I> PCI 1001, <I>Staphylococcus epidermidis</I> and <I>Staphylococcus aureus</I> 209 P, but in general the activity was inferior to that of 5-FU.<BR>2) Distribution<BR>By the intravenous administration of FT-207, 400mg/kg, in normal and AH-130 bearing rats, the concentration of FT-207 in serum and tissues maintained measurably until 16-24 hours.<BR>On the other hand, the active substances (5-FU, <I>etc</I>.) from FT-207 detected at 1-4 hours and peaked at 4-16 hours in tissues.<BR>3) Urinary excretion<BR>FT-207 and its active substances were excreted in urine for a long time, and the recoveries of FT-207 for 48 hours in rats, mice and rabbits were 12-18%.<BR>4) Metabolism<BR>In normal and AH-130 bearing rats, the main active substance from FT-207 administrated intravenously was 5-FU.