Research landscape of hydroxamic acid hybrids with therapeutic potential against prostate cancer: a decade of advances

Prostate cancer, a malignant tumor arising from the prostate gland, ranks as one of the most commonly diagnosed cancers in men globally and the eighth leading cause of cancer-related mortality worldwide. Hydroxamic acid derivatives, identified as outstanding histone deacetylase (HDAC) inhibitors, are a class of compounds with significant research interest in prostate cancer due to their diverse mechanisms of action, primarily involving epigenetic regulation and targeted enzyme inhibition. Recent studies highlight that incorporating diverse anti-prostate cancer pharmacophores with a hydroxamic acid moiety can potentiate their inhibitory efficacy against HDACs or endow them with multi-target HDAC inhibitory capabilities. Furthermore, hydroxamic acid hybrids possess inherent potential to enhance therapeutic efficacy through multi-target engagement, circumvent drug resistance via epigenetic reprogramming, improve pharmacokinetic profiles through structural optimization, and mitigate off-target toxicity through enhanced receptor selectivity, representing promising scaffolds for designing novel therapeutic candidates against prostate cancer. This review comprehensively outlines the research landscape of hydroxamic acid hybrids with therapeutic potential in prostate cancer, spanning from 2016 to the present, to uncover new avenues for discovering novel therapeutic candidates.