2-Pyridinyl-4(3H)-Quinazolinone: A Scaffold for Anti-influenza A Virus Compounds
2-Pyridinyl-4(3H)-Quinazolinone: A Scaffold for Anti-influenza A Virus Compounds
复制标题
2-吡啶基-4(3H)-喹唑啉酮：抗甲型流感病毒化合物的支架。
DOI：
10.1111/cbdd.12589
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发表时间：
2015-11-01
影响因子：
3
通讯作者：
Jiang, Tao
中科院分区：
文献类型：
--
作者：
Liu, Shixu;Wang, Wei;Jiang, Tao
合成了一系列2-pyridinyl-3-substituted-4(3H)-quinazolinones，并用细胞病变抑制法检测了它们的抗甲型流感病毒活性。大多数化合物具有较强的药效，其IC50值在51.6~93.0µM之间，优于目前市场上销售的药物利巴韦林。通过神经氨酸酶抑制实验、细胞内核因子-kappaB信号通路抑制实验和计算机对接，对新化合物的分子机制进行了研究。化合物4E是2-吡啶基-4(3H)-喹唑烷酮的N3咪唑-1-丙基取代的衍生物，在体外具有最强的抗甲型流感病毒活性，并抑制病毒神经氨酸酶和细胞内核因子-kappaB信号通路。综上所述，2-吡啶基-4(3 H)喹唑烷酮是一种新的骨架化合物，可用于设计有效的抗甲型流感病毒化合物，为解决流感耐药性问题提供了一种新的途径。
A series of 2-pyridinyl-3-substituted-4(3H)-quinazolinones were synthesized, and their anti-influenza A virus activities were determined using the cytopathic effect inhibition assay. Most of the compounds were potent with IC50 values ranging from 51.6 to 93.0 mu M, which are better than that of the currently marketed drug ribavirin. The molecular mechanisms of the new compounds were investigated using neuraminidase inhibition assay, cellular NF-kappa B signaling pathway inhibition assay, and computational docking. Compound 4e, which is a N3 imidazol-1-ylpropyl-substituted derivative of 2-pyridinyl-4(3H)-quinazolinone, had the most potent anti-influenza A virus activity in vitro, and inhibited both virus neuraminidase and cellular NF-kappa B signaling pathway. In conclusion, 2-pyridinyl-4(3H)quinazolinone is a new scaffold for the design of potent anti-influenza A virus compounds, offering an alternative approach to tackle influenza drug resistance.