Zhan Xiaoping, Xu Yun, Qi Qi, Wang Yaolin, Shi Huiying, Mao Zhenmin
School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, P. R. China.
Chem Biodivers. 2018 Mar;15(3):e1700513. doi: 10.1002/cbdv.201700513.
A series of novel quinazolinone derivatives containing a substituted amino moiety were synthesized, evaluated for their cytotoxic and antibacterial activities. The results of MTT assay showed that all synthesized target compounds 5A - 5O showed potent cytotoxicity against SGC-7901 (IC , 0.72 - 1.41 μm). Moreover, the compounds 5D, 5I, and 5K showed better selectivity as compared with positive controls pemetrexed and MTX due to weak cytotoxicity against normal tissue cell line HUVSMC. Among synthesized compounds, the compounds 5E, 5J, 5L, and 5N showed broad-spectrum cytotoxic activities against at least four cancer cell lines at a micromolar level. The results of antibacteria evaluation revealed that all synthesized compounds showed good to moderate antibacterial activities against Gram-negative bacteria Escherichia coli. Among them, the MIC values of the compounds 5C, 5F, and 5M were 0.31 μg/mL.
合成了一系列含有取代氨基部分的新型喹唑啉酮衍生物，并对其细胞毒性和抗菌活性进行了评估。MTT 测定结果表明，所有合成的目标化合物 5A - 5O 对 SGC - 7901 均表现出较强的细胞毒性（IC，0.72 - 1.41 μm）。此外，由于对正常组织细胞系 HUVSMC 的细胞毒性较弱，化合物 5D、5I 和 5K 与阳性对照培美曲塞和甲氨蝶呤相比表现出更好的选择性。在合成的化合物中，化合物 5E、5J、5L 和 5N 在微摩尔水平上对至少四种癌细胞系表现出广谱细胞毒性活性。抗菌评估结果表明，所有合成化合物对革兰氏阴性菌大肠杆菌均表现出良好至中等的抗菌活性。其中，化合物 5C、5F 和 5M 的 MIC 值为 0.3 μg/mL。
