8-Hydroxyquinoline, Derivatives and Metal-Complexes: A Review of Antileukemia Activities

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-kappa B), 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.

Automated summary

8-Hydroxyquinoline (8HQ) and its derivatives are metal-binding ligands capable of forming complexes with various biological activities. Our study summarizes the antileukemia activities of 8HQ compounds by discussing their mechanisms of action and compiling cytotoxicity data against different leukemia cell lines. The pharmacological activities of these compounds are mainly attributed to their metal coordination ability and interaction with multiple biological targets. We found consistent evidence that 8HQ exhibits promising proapoptotic features by directly interacting with DNA, inhibiting several targets, and inducing autophagy-associated cell death. These findings support the potential repositioning of 8HQ compounds for leukemia treatment, addressing the need for advances in therapeutic approaches.