Future medicinal chemistry · 2025
A comprehensive review on azole-based hydroxamic acid analogs as histone deacetylases (HDACs) inhibitors.
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Shukla Deepali, Matore Balaji Wamanrao, Murmu Anjali, Gawande Pragya, Roy Partha Pratim, Singh Jagadish
Аннотация
BACKGROUND: Histone deacetylases (HDAC) are essential epigenetic enzymes that modulate the remodeling of chromatin and transcriptional activity. Overexpression of HDAC has been associated with tumorigenesis, angiogenesis, metastasis, and therapeutic resistance.
METHODS: A systematic survey (2008-2025) evaluated the design, mechanism, and structure-activity relationships (SAR) of azole-based hydroxamic acid (ABHA) derivatives as histone deacetylase inhibitors (HDACIs).
RESULTS: ABHAs containing 1,3,4-oxadiazole, pyrazole, imidazole, triazole, indazole, thiadiazole, etc. Heterocyclic scaffolds show significant zinc-binding affinity, enhanced pharmacokinetics, and isoform-selective inhibition. Subtle structural variations in heteroaryl substituents, linker architecture, and hydroxamate coordination significantly modulate enzyme selectivity and cytotoxic efficacy.
CONCLUSION: ABHA hybrids provide versatile scaffolds with diverse activity for the rational development of next-generation, isoform-selective HDACIs with enhanced potency and therapeutic promise in anticancer drug design.
METHODS: A systematic survey (2008-2025) evaluated the design, mechanism, and structure-activity relationships (SAR) of azole-based hydroxamic acid (ABHA) derivatives as histone deacetylase inhibitors (HDACIs).
RESULTS: ABHAs containing 1,3,4-oxadiazole, pyrazole, imidazole, triazole, indazole, thiadiazole, etc. Heterocyclic scaffolds show significant zinc-binding affinity, enhanced pharmacokinetics, and isoform-selective inhibition. Subtle structural variations in heteroaryl substituents, linker architecture, and hydroxamate coordination significantly modulate enzyme selectivity and cytotoxic efficacy.
CONCLUSION: ABHA hybrids provide versatile scaffolds with diverse activity for the rational development of next-generation, isoform-selective HDACIs with enhanced potency and therapeutic promise in anticancer drug design.