State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Bioorg Med Chem. 2011 Aug 15;19(16):4895-902. doi: 10.1016/j.bmc.2011.06.061. Epub 2011 Jun 28.
A series of oxadiazole derivatives containing 1,4-benzodioxan (4a-4s) have been first synthesized for their potential immunosuppressive activity. Among the compounds, compound 4i showed the most potent biological activity against RAW264.7 cells (inhibition=37.66±2.34% for NO overproduction and IC(50)=0.05μM for iNOS). Docking simulation was performed to position compound 4i into the iNOS structure active site to determine the probable binding model. RT-PCR experiment results demonstrated that some of these compounds possessed good immunosuppressive activity against iNOS, especially for compound 4i. Therefore, compound 4i with potent inhibitory activity may be a potential agent.
首次合成了一系列含 1,4-苯并二恶烷（4a-4s）的噁二唑衍生物，以评估其潜在的免疫抑制活性。在所合成的化合物中，化合物 4i 对 RAW264.7 细胞的抑制活性最强（对 NO 生成的抑制率为 37.66±2.34%，对 iNOS 的半数抑制浓度为 0.05μM）。通过对接模拟将化合物 4i 定位到 iNOS 结构的活性位点，以确定可能的结合模型。RT-PCR 实验结果表明，这些化合物中的一些对 iNOS 具有良好的免疫抑制活性，特别是化合物 4i。因此，具有较强抑制活性的化合物 4i 可能是一种潜在的药物。
