Towards new C6-rigid S-DABO HIV-1 reverse transcriptase inhibitors: synthesis, biological investigation and molecular modeling studies.
Towards new C6-rigid S-DABO HIV-1 reverse transcriptase inhibitors: synthesis, biological investigation and molecular modeling studies.
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DOI：
10.1016/j.bmc.2013.08.040
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发表时间：
2013-11
影响因子：
3.5
通讯作者：
Hai-Qiu Wu;Zihong Yan;Wen‐xue Chen;Qiu-Qin He;Fener Chen;E. De Clercq;J. Balzarini;D. Daelemans;C. Pannecouque
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文献类型：
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作者：
Hai-Qiu Wu;Zihong Yan;Wen‐xue Chen;Qiu-Qin He;Fener Chen;E. De Clercq;J. Balzarini;D. Daelemans;C. Pannecouque
合成了一系列C6- rigids - dabo类似物，并在MT-4细胞培养中对野生型HIV-1株IIIB、双RT突变（K103N + Y181C）株RES056和HIV-2株ROD进行了生物学评价。大多数化合物表现出中等的抗病毒活性。其中化合物7q抗hiv -1活性最高，ec50值为0.26 μM，选择性指数（SI）为541。研究了这些newS-DABOs的初步构效关系（SAR），确定了靶RT并进行对接研究。
A series of C6-rigidS-DABO analogs characterized by a substituted benzoyl group at C6 position of the pyrimidine ring has been synthesized and biological evaluation as NNRTIs against wild-type HIV-1 strain IIIB, double RT mutant (K103N + Y181C) strain RES056 as well as HIV-2 strain ROD in MT-4 cell cultures. Most of the compounds exhibited moderate antiviral activities. Among them, compound7qdisplayed the highest anti-HIV-1 activity with an EC50value of 0.26 μM and a selectivity index (SI) of 541. The preliminary structure–activity relationship (SAR) of these newS-DABOs was investigated, the target RT was confirmed and docking study was performed.