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- W4311678051 abstract "Histone deacetylase 6 (HDAC6) is involved in multiple regulatory processes and emerges as a promising target for treating cancer and neurodegenerative diseases. Benefited from the unique sandwich conformation of ferrocene, a series of ferrocene-based hydroxamic acids have been developed as novel HDAC6 inhibitors in this paper, especially the two ansa-ferrocenyl complexes with IC50s at the nanomolar level. [3]-Ferrocenophane hydroxamic acid analog II-5 displays the most potent inhibitory activity on HDAC6 and establishes remarkable selectivity towards other HDAC isoforms. Compound II-5 dose-dependently induces accumulation of acetylated α-tubulin while having a negligible effect on the level of acetylated Histone H3, confirming its isoform selectivity. Further biological evaluation of II-5 on cancer cells corroborates its antiproliferative effect, which mainly contributed to the induction of cellular apoptosis. It is worth noting that compound II-5 demonstrates an optimal profile on human plasma stability. These results strengthen ferrocene's unique role in developing selective protein inhibitors and indicate that compound II-5 may be a suitable lead for further evaluation and development for treating HDAC6-associated disorders and diseases." @default.
- W4311678051 created "2022-12-28" @default.
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- W4311678051 date "2023-01-01" @default.
- W4311678051 modified "2023-09-30" @default.
- W4311678051 title "Synthesis and bioactivity evaluation of ferrocene-based hydroxamic acids as selective histone deacetylase 6 inhibitors" @default.
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- W4311678051 doi "https://doi.org/10.1016/j.ejmech.2022.115004" @default.
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