Current Landscape of Hydroxamic Acid Derivatives With Antileukemia Activity

Leukemia, as the second most prevalent hematological malignancy, could disrupt the production of healthy blood cells in the bone marrow, leading to anemia, neutropenia, and thrombocytopenia, and constitutes a significant global health burden. Chemotherapy remains a cornerstone of leukemia treatment, but drug resistance and severe adverse effects are the main culprits for its failure in treating leukemia, thereby creating an urgent imperative to develop innovative anti-leukemia agents. Hydroxamic acid derivatives, recognized as prominent histone deacetylase (HDAC) inhibitors, represent a promising class of agents in leukemia therapy, leveraging epigenetic modulation, multi-target activity, and synergistic potential to address unmet drug resistance and toxicity needs. This review summarizes the latest advancements in hydroxamic acid derivatives, including hydroxamic acid-azole hybrids, hydroxamic acid-indole hybrids, hydroxamic acid-pyridine/quinoline hybrids, and hydroxamic acid-(fused) pyrimidine hybrids, with therapeutic potential against leukemia, covering articles published from 2020 to the present. The structure–activity relationships and the mechanisms of action are also discussed to guide the rational design and development of more effective and less toxic therapeutic candidates.