Epigenetic regulation orchestrates
many cellular processes and
greatly influences key disease mechanisms. Histone deacetylase (HDAC)
enzymes play a crucial role either as biomarkers or therapeutic targets
owing to their involvement in specific pathophysiological pathways.
Beyond their well-characterized role as histone modifiers, HDACs also
interact with several nonhistone substrates and their increased expression
has been highlighted in specific diseases. The HDAC6 isoform, due
to its unique cytoplasmic localization, modulates the acetylation
status of tubulin, HSP90, TGF-β, and peroxiredoxins. HDAC6 also
exerts noncatalytic activities through its interaction with ubiquitin.
Both catalytic and noncatalytic functions of HDACs are being actively
studied in the field of specific rare disorders beyond the well-established
role in carcinogenesis. This Perspective outlines the application
of HDAC(6) inhibitors in rare diseases, such as Rett syndrome, inherited
retinal disorders, idiopathic pulmonary fibrosis, and Charcot–Marie–Tooth
disease, highlighting their therapeutic potential as innovative and
targeted disease-modifying agents.
Breakthroughs in AMP designing, peptide synthesis and biotechnology have shown promise in tackling this challenge and has revived the interest of using AMPs as an important weapon in fighting AMR.
The dynamic and crucial role of tubulin in different cellular functions rendered it a promising target in anticancer drug development. Combretastatin A-4 (CA-4), an inhibitor of tubulin polymerization isolated from natural sources, is a lead molecule with significant cytotoxicity against tumour cells. Owing to its non polar nature it exhibits low solubility in natural biological fluids, thereby prompting the development of new CA-4 based derivatives. The modification of this lead molecule was mostly carried out by keeping the crucial -orientation of the double bond intact, along with a trimethoxyphenyl aromatic ring, by employing different approaches. The issue of solubility was also addressed by the development of water soluble prodrugs of CA-4. The present review highlights the investigations into the parallel development of both new CA-4 based derivatives and prodrugs in the past few years.
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