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, 36 (17). pp. 3276-3283. ISSN 0276-7333

PDF - Accepted Version Download (1MB)

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:	21 Aug 2018 01:00
URI:	http://srodev.sussex.ac.uk/id/eprint/69611

View download statistics for this item

📧 Request an update