化学
组蛋白脱乙酰基酶
癌症研究
白血病
8-羟基喹啉
组蛋白
泛素
计算生物学
DNA
生物化学
生物
遗传学
基因
有机化学
作者
Carolina Bissani Gasparin,Diogo André Pilger
标识
DOI:10.1002/slct.202204219
摘要
Abstract 8‐Hydroxyquinoline and its derivatives consist of a group of metal‐binding ligands capable of reaching complexes that present several biological activities. In the present study, we collate and discuss data regarding the antileukemia activities of 8‐hydroxyquinoline (8HQ) compounds to provide an overview of their mechanisms of actions, and a compilation of cytotoxicity data against diverse leukemia cell lines. The pharmacological activities of this class of agents are associated primarily with their ability to coordinate metals and interact with multiple biological targets. We found consistent evidence that 8HQ exerts promising proapoptotic features through its direct interaction with deoxyribonucleic acid (DNA) and inhibition of multiple targets, such as the proteasome, nuclear factor kappa B (NF‐κB), histone deacetylase (HDAC), bromodomain and extra terminal (BET) proteins and janus kinases (JAKs), in addition to inducing autophagy associated cell death. Thus, we provide substantial evidence for the repositioning potential of the 8HQ class for the treatment of leukemia, a hematological malignancy for which urgent advances in therapeutic approaches are needed to overcome conventional therapy limitations.
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