Qiu Jingying, Xu Bixue, Gong Qineng, Pan Weidong, Liu Changxiao, Huang Zhengming, Gu Xiaoke, Liang Guangyi
Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, 221004, P. R. China.
The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, 202 Shachong South Road, Guiyang, 550002, P. R. China.
Chem Biodivers. 2016 Nov;13(11):1584-1592. doi: 10.1002/cbdv.201600113. Epub 2016 Nov 7.
A series of Matijin-Su (MTS, (2S)-2-{[(2S)-2-benzamido-3-phenylpropanoyl]amino}-3-phenylpropyl acetate) derivatives were synthesized and evaluated for their anti-HBV and cytotoxic activities in vitro. Six compounds (4g, 4j, 5c, 5g, 5h and 5i) showed significant inhibition against HBV DNA replication with the IC values in range of 2.18 - 8.55 μm, which were much lower than that of positive control lamivudine (IC 82.42 μm). In particular, compounds 5h (IC 2.18 μm; SI 151.59) and 5j (IC 5.65 μm; SI 51.16) displayed relatively low cytotoxicities, resulting in high SI values. Notably, besides the anti-HBV DNA replication activity, compound 4j also exhibited more potent in vitro cytotoxic activity than 5-fluorouracil in two hepatocellular carcinoma cell (HCC) lines (QGY-7701 and SMMC-7721), indicating that 4j may be a promising lead for the exploration of drugs with dual therapeutic effects on HBV infection and HBV-induced HCC.
合成了一系列马替金 - 苏（MTS，(2S)-2-{[(2S)-2-苯甲酰胺基-3-苯基丙酰基]氨基}-3-苯基丙基乙酸酯）衍生物，并对其体外抗乙肝病毒（HBV）和细胞毒性活性进行了评估。六种化合物（4g、4j、5c、5g、5h和5i）对HBV DNA复制表现出显著抑制作用，IC值在2.18 - 8.55μm范围内，远低于阳性对照拉米夫定（IC 82.42μm）。特别是，化合物5h（IC 2.18μm；SI 151.59）和5j（IC 5.65μm；SI 51.16）表现出相对较低的细胞毒性，从而具有较高的SI值。值得注意的是，除了抗HBV DNA复制活性外，化合物4j在两种肝癌细胞系（QGY - 7701和SMMC - 7721）中还表现出比5-氟尿嘧啶更强的体外细胞毒性活性，表明4j可能是探索对HBV感染和HBV诱导的肝癌具有双重治疗作用药物的一个有前景的先导化合物。
