Synthesis and biological evaluation of (±)-benzhydrol derivatives as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
Synthesis and biological evaluation of (±)-benzhydrol derivatives as potent non-nucleoside HIV-1 reverse transcriptase inhibitors.
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DOI：
10.1016/j.bmc.2011.07.003
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发表时间：
2011-08
影响因子：
3.5
通讯作者：
Xiaodong Ma;Xuan Zhang;Shi-qiong Yang;Huifang Dai;Liu-Meng Yang;Shuang‐Xi Gu;Yong-tang Zheng;
中科院分区：
文献类型：
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作者：
Xiaodong Ma;Xuan Zhang;Shi-qiong Yang;Huifang Dai;Liu-Meng Yang;Shuang‐Xi Gu;Yong-tang Zheng;
合成了一系列具有c环对位必需磺胺基的（±）-苯并羟基衍生物，并对其在C8166细胞中的潜在抗hiv活性进行了评价。大多数类似物对野生型HIV-1具有低浓度抑制活性，ec50值小于1μM。其中化合物7h的ec50值为0.12μM，选择性指数为312.73，是野生型HIV-1活性最高的抑制剂。部分菌株对双突变株A17（K103N+Y181C）的ec50值低于5μM，具有中等抑菌活性。此外，还探讨了这些衍生物与RT的结合模式和初步的构效关系，为进一步的化学修饰做准备。
A series of (±)-benzhydrol derivatives featuring the essential sulfonamide group at the para position on the C-ring were synthesized and evaluated for the potential anti-HIV activity in C8166 cells. Most of these analogues demonstrated low concentration inhibitory activity with EC50values less than 1μM against the wild-type HIV-1. In particular, compound 7h was identified as the highest active inhibitor of wild-type HIV-1 with an EC50value of 0.12μM and selectivity index value of 312.73. Furthermore, some of them also exhibited moderate activity against the double mutant strain A17(K103N+Y181C) with EC50values lower than 5μM. In addition, the binding modes with RT and the preliminary structure–activity relationships of these derivatives were also explored for further chemical modifications.