Novel naphthalene-enoates: Design and anticancer activity through regulation cell autophagy
Novel naphthalene-enoates: Design and anticancer activity through regulation cell autophagy
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新型萘烯酸盐：通过调节细胞自噬进行设计和抗癌活性
DOI：
10.1016/j.biopha.2019.108747
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发表时间：
2019
影响因子：
7.5
通讯作者：
Liu Xin Hua
中科院分区：
文献类型：
--
作者：
Yang Meng Di;Shen Xiao Bao;Hu Yang Sheng;Chen Yan Yan;Liu Xin Hua
设计合成了11种调节细胞自噬的二羟基-2-（1-羟基-4-甲基戊-3-烯基）萘衍生物。抗肿瘤活性结果表明，大多数化合物对GES-1和L-02具有明显的无毒作用，ic50在0.58 ~ 1.41 mM之间。其中，（S，Z）-1-（5,8-二羟基-1,4-二氧基-1,4-二氢萘-2-基）-4-甲基戊-3-烯基4-（3,4-二氢异喹啉-2(1 H)-基）-4-氧丁-2-烯酸酯（化合物4i）可诱导癌细胞凋亡。进一步实验表明，自噬作用在该化合物的促凋亡作用中起重要作用。初步机制表明，该化合物可通过自噬依赖的方式介导细胞凋亡，抑制磷酸肌苷3-激酶/蛋白激酶B和哺乳动物雷帕霉素靶蛋白（PI3K/AKT/mTOR）通路。
Eleven dihydroxy-2-(1-hydroxy-4-methylpent-3-enyl)naphthalene derivatives as anticancer agents through regulating cell autophagy were designed and synthesized. The anticancer activity results indicated that most compounds manifested obvious un-toxic effect on GES-1 and L-02 with IC50from 0.58 to 1.41 mM. Among them, (S,Z)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-enyl 4-(3,4-dihydroisoquinolin-2(1 H)-yl)-4-oxobut-2-enoate (compound4i)could induce cancer cells apoptosis. Further experiments showed that autophagy played an important role in the pro-apoptotic effect of this compound. Preliminary mechanism indicated that this compound could inhibit phosphoinositide 3-kinase/protein kinase B and the mammalian target of rapamycin (PI3K/AKT/mTOR) pathway by mediating apoptosis in an autophagy-dependent manner.