Organometallics
Organometallics
4 years ago

Pojamide: An HDAC3-Selective Ferrocene Analogue with Remarkably Enhanced Redox-Triggered Ferrocenium Activity in Cells

Pojamide: An HDAC3-Selective Ferrocene Analogue with Remarkably Enhanced Redox-Triggered Ferrocenium Activity in Cells
Justin M. Roberts, Supojjanee Sansook, Matthew Guille, John Spencer, Helfrid Hochegger, Peter Coxhead, Thomas G. Scott, Rhiannon Jones, Cory A. Ocasio, Simon J. Coles, Graham J. Tizzard, Nikolaos Tsoureas, James E. Bradner
A ferrocene containing o-aminoanilide, N1-(2-aminophenyl)-N8-ferrocenyloctanediamide (2b, Pojamide) displayed nanomolar potency vs HDAC3. In comparison 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 HDAC1,3 inhibition is desirable to achieve maximum anticancer 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.

Publisher URL: http://dx.doi.org/10.1021/acs.organomet.7b00437

DOI: 10.1021/acs.organomet.7b00437

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.