Synthesis and Biological Evaluation of Matijin-Su Derivatives as Potential Antihepatitis B Virus and Anticancer Agents
Synthesis and Biological Evaluation of Matijin-Su Derivatives as Potential Antihepatitis B Virus and Anticancer Agents
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作为潜在抗乙型肝炎病毒和抗癌药物的 Matijin-Su 衍生物的合成和生物学评价。
DOI：
10.1002/cbdv.201600113
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发表时间：
2016-11-01
影响因子：
2.9
通讯作者：
Liang, Guangyi
中科院分区：
文献类型：
--
作者：
Qiu, Jingying;Xu, Bixue;Liang, Guangyi
合成了一系列马蒂金素（MTS，（2S）-2-{[（2S）-2-苯甲酰氨基-3-苯丙酰基]氨基}-3-苯丙乙酸酯）衍生物，并对其体外抗HBV和细胞毒活性进行了评价。6个化合物（4g、4j、5c、5g、5 h和5i）对HBV DNA复制表现出明显的抑制作用，IC 50值在2.18 - 8.55 μ M范围内，远低于阳性对照拉米夫定（IC 50 82.42 μ M）。特别地，化合物5 h（IC 50 2.18 μ M; SI 151.59）和5 j（IC 50 5.65 μ M; SI 51.16）显示出相对低的细胞毒性，导致高SI值。值得注意的是，除了抗HBV DNA复制活性外，化合物4j还在两个肝细胞癌（HCC）细胞系（QGY-7701和SMMC-7721）中显示出比5-氟尿嘧啶更强的体外细胞毒活性，表明4j可能是探索对HBV感染和HBV诱导的HCC具有双重治疗作用的药物的有希望的先导物。
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 IC50 values in range of 2.18 - 8.55 mu M, which were much lower than that of positive control lamivudine (IC50 82.42 mu M). In particular, compounds 5h (IC50 2.18 mu M; SI 151.59) and 5j (IC50 5.65 mu M; 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.