Development of anti-HIV agents for the viral variants

开发针对病毒变种的抗 HIV 药物

• 批准号: 21590506
• 负责人: HOSHINO Tyuji
• 金额: $ 2.91万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590506/
• 关键词: 分子; 阻害剤開発; 変異体ウイルス; 薬剤耐性; シミュレーション; 分子動力学計算; プロテアーゼ阻害剤; 有機合成; 薬物設計; 合成経路

In order to produce the anti-HIV agents effective for the viral variants, we carried out in silico drug design, organic synthesis, and assay of the compound potency. The designed compounds were intended to be targeted on the I84V and V82A mutants of HIV-1 protease. Several compounds were synthesized, and some of the intermediates of the designed compounds showed anti-viral activity. It is required to enhance the compound potency greatly. Accordingly, the modification of the derivatives should be performed to produce a potent agent in our future work.

为了制备出对病毒变体有效的抗hiv药物，我们进行了硅基药物设计、有机合成和化合物效价测定。设计的化合物旨在靶向HIV-1蛋白酶的I84V和V82A突变体。合成了几种化合物，所设计化合物的一些中间体显示出抗病毒活性。需要大幅度提高复方效力。因此，在我们未来的工作中，应该对衍生物进行改性，以产生一种有效的药物。

项目成果

Structural and biochemical study on the inhibitory activity of derivatives of 5-nitro-furan-2-carboxylic acid for RNase H function of HIV-1 reverse transcriptase

• DOI: 10.1016/j.bmc.2010.12.011
• 发表时间: 2011-01-15
• 期刊: BIOORGANIC & MEDICINAL CHEMISTRY
• 影响因子: 3.5
• 作者: Yanagita, Hiroshi;Urano, Emiko;Hoshino, Tyuji
• 通讯作者: Hoshino, Tyuji

Structural and Energetic Analysis on the Complexes of Clinically Isolated Subtype C HIV-1 Proteases and Approved Inhibitors by Molecular Dynamics Simulation

• DOI: 10.1021/jp908314f
• 发表时间: 2010-01-14
• 期刊: JOURNAL OF PHYSICAL CHEMISTRY B
• 影响因子: 3.3
• 作者: Matsuyama, Shou;Aydan, Ay;Hoshino, Tyuji
• 通讯作者: Hoshino, Tyuji