Design, synthesis and antiviral activity of novel quinazolinones
Design, synthesis and antiviral activity of novel quinazolinones
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DOI：
10.1016/j.ejmech.2012.04.010
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发表时间：
2012-07-01
影响因子：
6.7
通讯作者：
Wang, Qingmin
中科院分区：
文献类型：
--
作者：
Wan, Ziwen;Wang, Mingxiao;Wang, Qingmin
HIV-1整合酶（IN）是抗病毒药物设计的有效治疗靶点。然而，出现的病毒株耐临床研究的IN抑制剂需要发现新的抑制剂，结构以及机制不同。本文设计并合成了一系列新型的喹唑啉酮类HIV-1抑制剂。新的合成路线为5-羟基喹唑啉酮类化合物的合成提供了一种实用的方法。初步生物活性测定结果表明，大部分喹唑啉酮类化合物具有抗HIV活性，其中化合物11b在10 μ M时抑制率为77.5%，是一个新的活性先导化合物。大部分化合物也表现出较好的抗TMV活性，其中化合物9a的抗TMV活性与商品化植物杀病毒剂利巴韦林相当。本工作为通过合理整合和优化已有的抗病毒药物，开发新型多功能抗病毒药物提供了一条新的有效途径。(C)2012年Elsevier Masson SAS。All rights reserved.
HIV-1 integrase (IN) is a validated therapeutic target for antiviral drug design. However, the emergence of viral strains resistant to clinically studied IN inhibitors demands the discovery of novel inhibitors that are structurally as well as mechanistically different. Herein, a series of quinazolinones were designed and synthesized as novel HIV-1 inhibitors. The new synthetic route provides a practical method for the preparation of 5-hydroxy quinazolinones. Primary bioassay results indicated that most of the quinazolinones possess anti-HIV activity, especially for compound 11b with 77.5% inhibition rate at 10 mu M emerged as a new active lead. Most of the synthesized compounds were also found to exhibit good anti-TMV activity, of which compound 9a showed similar in vivo anti-TMV activity to commercial plant virucide Ribavirin. This work provides a new and efficient approach to evolve novel multi-functional antiviral agents by rational integration and optimization of previously reported antiviral agents. (C) 2012 Elsevier Masson SAS. All rights reserved.