生物素
细胞毒性
化学
顺铂
癌细胞
组蛋白脱乙酰基酶
细胞凋亡
组蛋白脱乙酰酶抑制剂
药理学
生物化学
体外
癌症研究
癌症
组蛋白
DNA
生物
化疗
遗传学
作者
Weinan Han,Weiyu He,Yinglin Song,Jian Zhao,Zhiheng Song,Yi Shan,Wuyang Hua,Yanyan Sun
出处
期刊:Dalton Transactions
[The Royal Society of Chemistry]
日期:2022-01-01
卷期号:51 (18): 7343-7351
被引量:6
摘要
Despite the wide clinical use of platinum drugs in cancer treatment, their severe side effects and lack of tumor selectivity seriously limit their further clinical application. To address the limitations of the current platinum drugs, herein a multifunctional platinum(IV) compound 1 containing a histone deacetylase (HDAC) inhibitor (4-phenylbutyric acid, 4-PBA) and a tumor-targeting group (biotin) has been designed and prepared. An in vitro cytotoxicity study indicated that compound 1 exhibits comparable or superior cytotoxicity to cisplatin against the tested cancer cell lines, but greatly reduced toxicity in human normal liver LO2 cells, implying the potential tumor-targeting ability of compound 1. Molecular docking results indicate that compound 1 can effectively interact with a biotin-specific receptor (streptavidin) through its biotin moiety, enabling potential tumor-targeting capability. Further studies indicated that compound 1's cytotoxicity stems from inducing DNA damage via the mitochondrial apoptotic pathway and inhibiting HDACs. Consequently, this compound can not only take advantage of the tumor selectively of biotin to improve its tumor-targeting ability but also strengthen its anticancer activity via simultaneously targeting DNA and HDACs.
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