Design, synthesis, biological activities and 3D-QSAR studies of quinazolinone derivatives containing hydrazone structural units
Design, synthesis, biological activities and 3D-QSAR studies of quinazolinone derivatives containing hydrazone structural units
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含腙结构单元的喹唑啉酮衍生物的设计、合成、生物活性及3D-QSAR研究
DOI：
10.1039/d0nj05450j
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发表时间：
2021-03-14
影响因子：
3.3
通讯作者：
Ouyang, Gui-Ping
中科院分区：
文献类型：
--
作者：
Shao, Li-Hui;Fan, Si-Li;Ouyang, Gui-Ping
本研究设计并合成了三个系列含腙结构的喹唑啉酮衍生物。生物活性实验表明，这些化合物对人肺癌细胞（A549）和人前列腺癌细胞（PC-3）具有良好的抗肿瘤活性，对非致瘤性大鼠肾小管上皮细胞（NRK-52E）无明显毒性。其中化合物7n对A549和PC-3表现出较强的抑制活性，IC50分别为7.36和7.73 μ mol L-1。随后，讨论了化合物结构与多种生物活性之间的关系。通过CoMFA建立了一个良好的预测三维定量构效关系（3D-QSAR）模型，以指导未来的结构单元。目前的结果强烈表明，引入2-氟苯甲酰的7n可以作为开发新型抗肿瘤药物的先导化合物。
In this study, three series of quinazolinone derivatives containing hydrazone structures were designed and synthesized. Bioactivity assays indicated that these compounds showed good antitumour activities towards human lung cancer cells (A549) and human prostate cancer cells (PC-3) and no apparent toxicity towards those nontumorigenic rat renal tubular epithelial cells (NRK-52E). In particular, compound 7n showed potent inhibitory activity towards A549 and PC-3 with IC50 of 7.36 and 7.73 mu mol L-1, respectively. Subsequently, the relationships between the compound structures and numerous biological activities are discussed. A good predictive three-dimensional quantitative structure-activity relationship (3D-QSAR) model was constructed via CoMFA to direct the future structural units. The present results strongly show that 7n with the introduction of 2-fluorobenzoyl should be considered as a lead compound to develop novel antitumour agents.