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6-氨基喹诺酮对HIV具有完全不同于已知抗HIV药物的作用机制,其先导物WM5对HIV-1复制周期中的关键步骤——Tat介导的长末端重复序列的转录具有抑制作用。在WM5结构的基础上,人们设计和合成了各种系列的6-氨基喹诺酮衍生物。抗病毒活性测定结果表明,衍生物26c,26e,26i和26j对HIV具有很强的抑制作用,对MT-4,PBMCs和CEM细胞系的EC50为0.0087～0.7μg/mL,并具有阳性S1,其中26e和26i对CEM细胞系的S1>1000。加入时间试验证实了6-氨基喹诺酮的作用机制,即抑制HIV复制周期中的整合后阶段。此外,本文初步总结了6-氨基喹诺酮对HIV的构-效关系和结构-细胞毒性关系。
6-Aminoquinolones have a completely different mechanism of action on HIV than known anti-HIV drugs and lead WM5 has an inhibitory effect on the transcription-critical Tat-terminal long-terminal repeat, a key step in HIV-1 replication cycle. Based on the WM5 structure, various series of 6-aminoquinolone derivatives have been designed and synthesized. The results of antiviral activity assay showed that derivatives 26c, 26e, 26i and 26j had a strong inhibitory effect on HIV, EC50 of 0.0087 ~ 0.7μg / mL for MT-4, PBMCs and CEM cell lines, Where 26e and 26i on the CEM cell line S1> 1000. The addition of time trial confirms the mechanism of action of 6-aminoquinolone, which inhibits the post-integration phase of the HIV replication cycle. In addition, the structure-cytotoxicity of 6-Aminoquinolones to HIV was initially summarized.