Pojamide: An HDAC3-selective ferrocene analogue with remarkably enhanced redox-triggered ferrocenium activity in cells.

Ocasio, Tony, Sansook, Supojjanee, Jones, Alice Rhiannon, Roberts, Justin, Scott, Thomas, Tsoureas, Nikolaos, Coxhead, Peter, Guille, Matthew, Tizzard, Graham J, Coles, Simon J, Hochegger, Helfrid, Bradner, James E and Spencer, John (2017) Pojamide: An HDAC3-selective ferrocene analogue with remarkably enhanced redox-triggered ferrocenium activity in cells. Organometallics. ISSN 0276-7333 (Accepted)

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Abstract

A ferrocene containing ortho-aminoanilide, N1-(2-aminophenyl)-N8-ferrocenyloctanediamide, 2b (Pojamide) displayed nanomolar potency vs. HDAC3. Compared to RGFP966, a potent and selective HDAC3 inhibitor, Pojamide displayed superior activity in HCT116 colorectal cancer cell invasion assays; however, TCH106 and Romidepsin, potent HDAC1 inhibitors, outperformed Pojamide in cellular proliferation and colony formation assays. Together, these data suggest that HDAC 1 & 3 inhibition is desirable to achieve maximum anti-cancer benefits. Additionally, we explored Pojamide-induced redox-pharmacology. Indeed, treating HCT116 cells with Pojamide, SNP (sodium nitroprusside) and glutathione (GSH) led to greatly enhanced cytotoxicity and DNA damage attributed to activation to an Fe(III) species.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science > QD Chemistry > QD0146 Inorganic chemistry
Q Science > QD Chemistry > QD0241 Organic chemistry
Q Science > QD Chemistry > QD0241 Organic chemistry > QD0411 Organometallic chemistry and compounds
Depositing User: John Spencer
Date Deposited: 10 Aug 2017 11:42
Last Modified: 12 Aug 2017 01:52
URI: http://sro.sussex.ac.uk/id/eprint/69611

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