Anti-HIV diarylpyrimidine-quinolone hybrids and their mode of action.
Anti-HIV diarylpyrimidine-quinolone hybrids and their mode of action.
复制标题
DOI：
10.1016/j.bmc.2015.03.037
复制
发表时间：
2015-07
影响因子：
3.5
通讯作者：
Tian-Qi Mao;Qiu-Qin He;Zheng-Yong Wan;Wen‐xue Chen;Fener Chen;Gang-Feng Tang;E. De Clercq;D. Daelemans;C. Pannecouque
中科院分区：
文献类型：
--
作者：
Tian-Qi Mao;Qiu-Qin He;Zheng-Yong Wan;Wen‐xue Chen;Fener Chen;Gang-Feng Tang;E. De Clercq;D. Daelemans;C. Pannecouque
分子杂交方法是设计具有改进的亲和力和功效的新分子的有力工具。在此背景下，合成了一系列二芳基嘧啶-喹诺酮杂合体，并针对野生型HIV-1和突变病毒株进行了评价。最具活性的杂交体5a显示出对HIV-1 IIIB的EC 50值为0.28 ± 0.07 μM。几种基于酶的测定清楚地指出了RT靶向的作用机制。对接研究表明，这些杂交体可以很好地定位在HIV-1 RT的NNIBP中，尽管分子中喹诺酮3-羧酸部分具有庞大和极性的性质。
A molecular hybridization approach is a powerful tool in the design of new molecules with improved affinity and efficacy. In this context, a series of diarylpyrimidine–quinolone hybrids were synthesized and evaluated against both wt HIV-1 and mutant viral strains. The most active hybrid5adisplayed an EC50value of 0.28 ± 0.07 μM against HIV-1 IIIB. A couple of enzyme-based assays clearly pinpoint a RT-targeted mechanism of action. Docking studies revealed that these hybrids could be well located in the NNIBP of HIV-1 RT despite the bulky and polar properties of a quinolone 3-carboxylic acid moiety in the molecules.