Specific Nonpeptide Inhibitors of Puromycin-Sensitive Aminopeptidase with a 2,4(1H,3H)-Quinazolinedione Skeleton

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概要

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• Potent, specific, chemically stable and non-peptide/small-molecular inhibitors of puromycin-sensitive aminopeptidase, such as 3-(2,6-diethylphenyl)-2,4(1H,3H)-quinazolinedione (PAQ-22, 5), were prepared by the structural development of a potent PSA inhibitor, 2-(2,6-diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (PIQ-22,4). The design was carried out partly by applying electrostatic potential field information obtained from PIQ-22 (4) and its derivatives based on thalidomide (2). This information revealed that a positive electrostatic potential field around the benzylic methylene in the tetrahydroisoquinoline ring is necessary for potent activity. Lineweaver-Burk plot analysis showed that PAQ-22 (5) and its derivatives inhibit puromycin-sensitive aminopeptidase (PSA) in a non-competitive manner. These potent and specific PSA inhibitors showed dose-dependent cell invasion-inhibitory activity in a Matrigel assay using mouse melanoma B16F10/L5 cells, in spite of their low cell toxicity.

• 公益社団法人日本薬学会の論文
• 2003-11-01

著者

• 棚谷 綾

  お茶の水女子大・理

• 棚谷 綾

  お茶の水女子大学大学院人間文化創成科学研究科理学専攻/先端融合部門

• Kagechika Hiroyuki

  Graduate School Of Pharmaceutical Sciences The University Of Tokyo:research Foundation Itsuu Laborat

• Kagechika Hiroyuki

  Graduate School Of Biomedical Sci. Tokyo Medical And Dental Univ.

• HASHIMOTO Yuichi

  Institute of Molecular & Cellular Biosciences, The University of Tokyo

• Hashimoto Yuichi

  Univ. Tokyo Tokyo Jpn

• Nagasawa K

  Institute Of Molecular And Cellular Biosciences The University Of Tokyo

• Nagasawa Kazuo

  Institute Of Molecular And Cellular Biosciences The University Of Tokyo

• Hashimoto Y

  Graduate School Of Pharmaceutical Sciences Kyushu University

• TANATANI Aya

  Faculty of Pharmaceutical Sciences, University of Tokyo

• TANATANI Aya

  Institute of Molecular and Cellular Biosciences, The University of Tokyo

• Hashimoto Yuichi

  Institute Of Molecular & Cellular Biosciences University Of Tokyo

• Hashimoto Yuichi

  Institute Of Molecular And Cellular Biosciences The Universityv Of Tokyo

• Kobayashi Hisayoshi

  Institute Of Molecular And Cellular Biosciences University Of Tokyo

• Tanatani A

  Institute Of Molecular And Cellular Biosciences The University Of Tokyo

• KAKUTA Hiroki

  Institute of Molecular & Cellular Biosciences, The University of Tokyo

• Kagechika H

  Tokyo Medical And Dental Univ. Tokyo Jpn

• Nagasawa Kazuki

  Institute Of Molecular And Cellular Biosciences The University Of Tokyo

• Hashimoto Y

  Institute Of Molecular & Cellular Biosciences The University Of Tokyo

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