AI Article Synopsis
- Histone deacetylase inhibitors (HDACi) are being explored as potential treatments for neurodegenerative diseases, cancer, and rare disorders.
- The study focuses on the creation of spiroindoline-based HDAC6-selective inhibitors, identifying one compound as the most effective in the series.
- Biological tests showed these compounds can inhibit cancer cell growth and trigger apoptosis through specific molecular actions, such as increasing tubulin acetylation and affecting pSTAT3 levels.
Article Abstract
Histone deacetylase inhibitors (HDACi) have emerged as promising therapeutics for the treatment of neurodegeneration, cancer, and rare disorders. Herein, we report the development of a series of spiroindoline-based HDAC6 isoform-selective inhibitors based on the X-ray crystal studies of the hit . We identified compound as the most potent and selective HDAC6 inhibitor of the series. Biological investigation of compounds , , and demonstrated their antiproliferative activity against several cancer cell lines. Western blotting studies indicated that they were able to increase tubulin acetylation, without significant variation in histone acetylation state, and induced PARP cleavage indicating their apoptotic potential at the molecular level. induced HDAC6-dependent pSTAT3 inhibition.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667836 | PMC |
| http://dx.doi.org/10.1021/acsmedchemlett.0c00395 | DOI Listing |
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