Pojamide organometallics with corrected Fig and ORCIDs.pdf (1.06 MB)
Pojamide: An HDAC3-selective ferrocene analogue with remarkably enhanced redox-triggered ferrocenium activity in cells.
journal contributionposted on 2023-06-09, 07:32 authored by Tony Ocasio, Supojjanee Sansook, Alice Rhiannon Jones, Justin Roberts, Thomas Scott, Nikolaos Tsoureas, Peter Coxhead, Matthew Guille, Graham J Tizzard, Simon J Coles, Helfrid HocheggerHelfrid Hochegger, James E Bradner, John SpencerJohn Spencer
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.
Exploiting chemical genetics to investigate the control of microtubule dynamics by mitotic kinases; G0900; CANCER RESEARCH UK; C28206/A14499
- Accepted version
PublisherAmerican Chemical Society
Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
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