Design, synthesis and biological evaluation of novel asperphenamate derivatives
Design, synthesis and biological evaluation of novel asperphenamate derivatives
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新型阿斯芬那酯衍生物的设计、合成及生物学评价
DOI：
10.1016/j.ejmech.2016.01.020
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发表时间：
2016-03-03
影响因子：
6.7
通讯作者：
Yuan, Lei
中科院分区：
文献类型：
--
作者：
Liu, Qingyin;Li, Wei;Yuan, Lei
设计合成了一系列新型的氨酚甲酸酯类化合物，包括系列I(芳香族杂环取代的A-苯基)和系列II(磺酰基取代的酰基)。用标准的四甲基偶氮唑盐比色法筛选了所有化合物对MCF-7、HeLa和BEL-7402细胞株的体外抗增殖活性。构效关系研究表明，杂环类型在活性中起重要作用。6元环衍生物比5元环具有更强的活性，A环区的磺酰基对活性有重要贡献。在所有的衍生物中，对甲苯磺酰衍生物8c在三个人类癌细胞系中显示出最大的效力。尤其是在MCF-7细胞中，8c的细胞效力约为顺铂的3.0倍。首先，研究了SC诱导MCF-7细胞死亡的机制。结果表明，细胞死亡是由自噬诱导的，而不是由细胞凋亡或细胞周期停滞引起的。进一步研究表明，8c可诱导HeLa和BEL-7402细胞自噬细胞死亡。(C)2016年爱思唯尔·马森SAS。版权所有。
A series of novel asperphenamate derivatives were designed and synthesized, including series I (the A-phenyl group replaced with various aromatic heterocycles) and series II (the acyl group substituted by sulfonyl group). All compounds have been screened for their antiproliferative activity in vitro against MCF-7, HeLa, and BEL-7402 cell lines by the standard MTT method. Structure-activity relationship studies displayed the heterocycle type played an important role in activity. Six-membered ring derivatives displayed more potency than five-membered ring and the sulfonyl group in A-ring region made an important contribution to activity. Among all derivatives, tosyl derivative 8c exhibited the greatest potency in three human cancer cell lines. Especially in MCF-7 cells, the cellular potency of 8c was approximately 3.0-fold more potent than that of cisplatin. Firstly, the mechanism of cell death induced by Sc in MCF-7 cells was investigated. The results showed that the cell death was induced by autophagy instead of apoptosis or cell cycle arrest. Further studies indicated that 8c might induce autophagic cell death in HeLa and BEL-7402 cell lines. (C) 2016 Elsevier Masson SAS. All rights reserved.