Selevtive Nonpeptidic Inhibitors of Herpes Simplex Virus Type 1 and Human Cytomegalovirus Proteases

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概要

• 論文の詳細を見る

• The proteases encoded by herpesviruses including herpes simplex type 1(HSV-1)and human cytomegalovirus(HCMV)are attractive targets for antiviral drug development because of their important roles in viral replication. We randomly screened a chemical compound library for inhibitory activity against HSV-1 protease. 1, 4-Dyhydroxynaphthalene and three naphthoquinones were found to be potent inhibitors of HSV-1 protease with IC_<50> values of 6.4 to 16.9μм. Inhibitory mode analysis of the compounds against HSV-1 protease suggested that, in spite of structural similarities, only 1, 4-dihydroxynaphthalene was competitive inhibitor, whereas the three naphthoquinones were noncompetitive inhibitors. Among all assayed dihydrocynaphthalene dericatives in the chemical compound library, 1, 4-dihydroxynaphthalene proved to be the most potent inhibitor of HSV-1 protease. Therefore, the two hydroxyl groups located at positions 1 and 4 on the naphthalene structure seemed essential for exertion of a potent inhibitors activity against HSV-1 protease. In addition, we have found that these compounds are also potent inhibitors of HCMV protease with extremel low micromolar IC_<50> values. This differed from the results of inhibitory mode analysis of HSV-1 protease, 1, 4-dihydroxynaphthalene was a noncompetitive inhibitor of HCMV protease, and three naphthoquinones were competitive inhibitors. These compounds showed no effective activity against several mammalian serine proteases(trypsin, chymotrypsin, kallikrein, plasmin, thrombin and Factor Xa)at 100μм. These results suggest that 1, 4-dihydroxynaphthalene and three naphthoquinones may be useful in the development of nonpeptidic antiherpesvirus agents.

• 公益社団法人日本薬学会の論文
• 2001-03-01

著者

• Matsumoto M

  Osaka Medical Center For Cancer And Cardiovascular Diseases Osaka

• Matsumoto Misako

  Department Of Immunology Osaka Medical Center For Cancer And Cardiovascular Diseases

• HAYASHI Hideya

  Pharmaceuticals and Biotechnology Laboratory, Japan Energy Corporation

• Hayashi H

  Univ. Tokyo Tokyo Jpn

• Hayashi H

  Drug Research Division Dainippon Sumitomo Pharma Co. Ltd.

• Hayashi Hideya

  Pharmaceuticals And Biotechnology Laboratory Japan Energy Corporation

• Hayashi H

  Pharmaceuticals & Biotechnology Laboratory Japan Energy Corporation

• Hayashi Hideya

  Pharmaceuticals & Biotechnology Laboratory Japan Energy Corporation

• TAKAKU Haruo

  Drug Research Division, Dainippon Sumitomo Pharma Co., Ltd.

• MATSUMOTO Mitsuhiro

  Pharmaceuticals and Biotechnology Laboratory, Japan Energy Corporation

• MISAWA Satoru

  Pharmaceuticals and Biotechnology Laboratory, Japan Energy Corporation

• CHIBA Nobuyoshi

  Pharmaceuticals and Biotechnology Laboratory, Japan Energy Corporation

• TAKAKU Haruo

  Pharmaceuticals and Biotechnology Laboratory, Japan Energy Corporation

• Matsumoto Mitsuharu

  Takeda Chemical Industries Ltd. Pharmaceutical Research Division

• Takaku H

  Drug Research Division Dainippon Sumitomo Pharma Co. Ltd.

• Misawa Satoru

  Pharmaceuticals & Biotechnology Laboratory Japan Energy Corporation

• Misawa S

  Pharmaceuticals And Biotechnology Laboratory Japan Energy Corporation

• Chiba Nobuyoshi

  Pharmaceuticals And Biotechnology Laboratory Japan Energy Corporation

• Takaku Haruo

  Pharmaceuticals And Biotechnology Laboratory Japan Energy Corporation

• Matsumoto Mitsuhiro

  Pharmaceuticals & Biotechnology Laboratory Japan Energy Corporation

• Matsumoto Mitsuhiro

  First Department Of Internal Medicine Kumamoto University School Of Medicine

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