Inhibitory Effects of Tetrandrine and Related Synthetic Compounds on Angiogenesis in Streptozotocin-Diabetic Rodents

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概要

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• Structure-activity relationships of tetrandrine, isolated from a Kampo medicine, Stephania tetrandrae S. MOORE (root), and related synthetic compounds, were investigated in in vitro fetal bovine serum (FBS)-stimulated angiogenesis of cultured choroids in streptozotocin-diabetic Wistar rats, and air-pouch granuloma angiogenesis in vivo in diabetic mice. Tetrandrine, KS-1-1 (6,7-dimethoxy-1-[[4-[5-(6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinolinyl)methyl-2-methoxy]phenoxy]benzol]-2-methyl-1,2,3,4-tetrahydroisoquinoline), and KS-1-4 (6,7-dimethoxy-1-[[4-[4-(6,7-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinolinyl)methyl]phenoxy]benzyl]-2-methyl-1,2,3,4-tetrahydroisoquinoline), potently inhibited choroidal angiogenesis and air-pouch granuloma angiogenesis in the diabetic state. Their inhibitory effects on diabetic choroids were greater than those on normal choroids. Among these compounds, KS-1-4 inhibited only diabetic angiogenesis. These compounds significantly inhibited FBS-stimulated tube formation in vascular endothelial cells from normal rats. Tetrandrine and KS-1-4,but not KS-1-1,inhibited vascular endothelial growth factor- and platelet-derived growth factor-BB-stimulated angiogenesis in normal choroids. The bis[tetrahydroisoquinoline] moiety, connected by oxy-bis[phenylenemethylene]and 2,2'-diemthyl groups in tetrandrine, contribues to the inhibition of diabetic choroidal angiogenesis. KS-1-4 may be a candidate for anti-choroidopathy and retinopathy drugs in the diabetic state.

• 社団法人日本薬学会の論文
• 1999-04-15

著者

• 木村 郁子

  富山医薬大薬薬品作用学

• 木村 郁子

  富山医科薬科大学

• 木村 郁子

  富山医科薬科大学 臨床薬理学

• 木村 郁子

  富山医科薬科大学大学院薬学研究科臨床薬理学

• 木村 郁子

  富山医科薬科大学 大学院薬学研究科臨床薬理学講座

• KIMURA Ikuko

  Department of Chemical Pharmacology Faculty of Pharmaceutical Sciences, Toyama medical and Pharmaceu

• Kimura M

  Health Science Center At San Antonio The University Of Texas

• KOBAYASHI Shinjiro

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University

• FUKUTA Mizuki

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University

• KONTANI Hitoshi

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University

• INABA Kazuhiko

  Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmace

• NIWA Masashi

  Santen Pharmaceuticals Co. LTD.

• MITA Shiro

  Santen Pharmaceuticals Co. LTD.

• KIMURA Masayasu

  Health Science Center at San Antonio, The University of Texas

• Niwa Masashi

  北陸大学 薬 薬理

• Fukuta Mizuki

  Department Of Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University

• Fukuta Mizuki

  北陸大学 薬 薬理

• Inaba Kazuhiko

  Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceut

• Inaba Kazuhiko

  北陸大学 薬 薬理

• Kontani H

  Department Of Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University

• Kontani H

  Hokuriku Univ. Kanazawa Jpn

• Mita S

  Santen Pharmaceutical Co. Ltd. Osaka Jpn

• Kimura I

  Toyama Medical And Pharmaceutical Univ. Toyama Jpn

• Kimura Ikuko

  Department Of Chemical Pharmacology Faculty Of Phrmaceutical Sciemes Toyama Medical And Pharmaceutic

• Kimura M

  Tsumura & Co. Ltd. Ibaraki Jpn

• Kimura Masayasu

  Department Of Chemical Pharmacology Faculty Of Phrmaceutical Sciemes Toyama Medical And Pharmaceutic

• Kimura I

  Department Of Ophthalmology Keio University School Of Medicine

• 木村 郁子

  富山医科薬科大学 薬学部 薬品作用学

• Kimura Ikuko

  Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceut

• Kimura Masayasu

  Health Science Center At San Antonio The University Of Texas

• Kobayashi Shinjiro

  Department Of Chemical Pharmacology Toyama Medical And Pharmaceutical University

• Kontani Hitoshi

  Department Of Pharmacology Faculty Of Pharmaceutical Science Hokuriku University

• Inaba K

  Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceut

• Kobayashi S

  Kyoritsu Coll. Pharmacy

• 木村 郁子

  Department Of Clinical Pharmacology Graduate School Of Pharmaceutical Sciences Toyama Medical And Ph

• Kimura Ikuko

  Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Toyama Medical & Pharmace

• Kobayashi Shinjiro

  Department Of Clinical Pharmacology Faculty Of Pharmaceutical Sciences Hokuriku University:organizat

• Fujihara Mitsuhiro

  Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceut

• Kimura Ikuko

  Deparment Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences Toyama Medical And Pharmaceutical University

• 木村 郁子

  Department of Food and Nutrition Science, Toyama College

• 木村 郁子

  富山医科薬科大学大学院薬学研究科 臨床薬理学講座

• KONTANI Hitoshi

  Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Nagoya City University

• Kontani Hitoshi

  Departmenr of Pharmacology, Faculty of Pharmaceutical Science, Hokuriku University

• Kobayashi Shinjiro

  Department of Applied Chemistry, Faculty of Engineering, Kyushu University

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