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 contribution
posted 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 SpencerA 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.
Funding
Exploiting chemical genetics to investigate the control of microtubule dynamics by mitotic kinases; G0900; CANCER RESEARCH UK; C28206/A14499
History
Publication status
- Published
File Version
- Accepted version
Journal
OrganometallicsISSN
0276-7333Publisher
American Chemical SocietyExternal DOI
Issue
17Volume
36Page range
3276-3283Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2017-08-10First Open Access (FOA) Date
2018-08-21First Compliant Deposit (FCD) Date
2017-08-04Usage metrics
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