Novel Nitrogen Heterocycle-Hydroxamic Acid Conjugates Demonstrating Potent Anti-Acute Lymphoblastic Leukemia Activity: Induction of Endogenous Apoptosis and G0/G1 Arrest via Regulation of Histone H3 Acetylation and AKT Phosphorylation in Jurkat Cells.

ABSTRACT: Epigenetics garnered significant scientific interest in recent decades, with histone acetylation emerging as the most prevalent epigenetic deregulation process observed in malignancies. The clinical application of histone deacetylase (HDAC) inhibitors faced challenges, including complex therapeutic mechanisms and inconsistent treatment outcomes. In Acute Lymphoblastic Leukemia (ALL), the dysregulation of HDAC activity presents a promising therapeutic target. To investigate cellular-level tumor suppression by HDAC inhibitors possessing potent target engagement, we developed two novel azetidine-hydroxamic acid conjugates. Compared to N-hydroxy-4-((quinolin-4-ylamino)methyl)benzamide (NBU-1), N-hydroxy-6-((5-methyl-4-nitro-9-oxo-9,10-dihydroacridin-1-yl)amino)hexanamide (NBU-2) demonstrated e

SUBMITTER: Wu L 

PROVIDER: S-EPMC12651750 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature