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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
Pojamide: An HDAC3-selective ferrocene analogue with remarkably enhanced redox-triggered ferrocenium activity in cells
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.
0276-7333
3276–3283
Ocasio, Cory A.
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Sansook, Supojjanee
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Jones, Rhiannon
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Roberts, Justin M.
7c5970cc-d6cf-4d77-b82a-0995c320e23e
Scott, Thomas G.
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Tsoureas, Nikolaos
b40771a1-8870-43bc-8989-3c6eee2f325f
Coxhead, Peter
7d49795f-0a1b-416c-a61b-b367be46ae8d
Guille, Matthew
dfefb828-7c5b-4529-8df6-d7a10d8d5b67
Tizzard, Graham J.
8474c0fa-40df-43a6-a662-7f3c4722dbf2
Coles, Simon J.
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Hochegger, Helfrid
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Bradner, James E.
b728f11e-9cce-492c-9b53-3a875eab706d
Spencer, James
e1c8688f-4021-43ea-a92a-2ec703543fa0
Ocasio, Cory A.
c602892b-77e3-4e2c-9eaf-9f5dbfa5b90d
Sansook, Supojjanee
b5e89a15-b73e-4b73-b985-e0725f3f4d8a
Jones, Rhiannon
fbedec48-be90-47f5-a1f8-bb50c1e8602d
Roberts, Justin M.
7c5970cc-d6cf-4d77-b82a-0995c320e23e
Scott, Thomas G.
ca2696a1-8a04-4241-a0dd-3de2521949cc
Tsoureas, Nikolaos
b40771a1-8870-43bc-8989-3c6eee2f325f
Coxhead, Peter
7d49795f-0a1b-416c-a61b-b367be46ae8d
Guille, Matthew
dfefb828-7c5b-4529-8df6-d7a10d8d5b67
Tizzard, Graham J.
8474c0fa-40df-43a6-a662-7f3c4722dbf2
Coles, Simon J.
3116f58b-c30c-48cf-bdd5-397d1c1fecf8
Hochegger, Helfrid
10705b48-bd20-488d-bdc5-64860803c070
Bradner, James E.
b728f11e-9cce-492c-9b53-3a875eab706d
Spencer, James
e1c8688f-4021-43ea-a92a-2ec703543fa0

Ocasio, Cory A., Sansook, Supojjanee, Jones, Rhiannon, Roberts, Justin M., Scott, Thomas G., Tsoureas, Nikolaos, Coxhead, Peter, Guille, Matthew, Tizzard, Graham J., Coles, Simon J., Hochegger, Helfrid, Bradner, James E. and Spencer, James (2017) Pojamide: An HDAC3-selective ferrocene analogue with remarkably enhanced redox-triggered ferrocenium activity in cells. Organometallics, 36 (17), 3276–3283. (doi:10.1021/acs.organomet.7b00437).

Record type: Article

Abstract

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.

Text
Pojamide organometallics with corrected Fig and ORCIDs - Accepted Manuscript
Available under License University of Southampton Accepted Manuscript Licence.
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Accepted/In Press date: 3 August 2017
e-pub ahead of print date: 21 August 2017
Published date: 11 September 2017

Identifiers

Local EPrints ID: 413525
URI: http://eprints.soton.ac.uk/id/eprint/413525
DOI: doi:10.1021/acs.organomet.7b00437
ISSN: 0276-7333
PURE UUID: 3cac6679-dbeb-4c16-99d1-d3b3a43c620a
ORCID for Graham J. Tizzard: ORCID iD orcid.org/0000-0002-1577-5779
ORCID for Simon J. Coles: ORCID iD orcid.org/0000-0001-8414-9272

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Date deposited: 25 Aug 2017 16:31
Last modified: 16 Mar 2024 05:40

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Contributors

Author: Cory A. Ocasio
Author: Supojjanee Sansook
Author: Rhiannon Jones
Author: Justin M. Roberts
Author: Thomas G. Scott
Author: Nikolaos Tsoureas
Author: Peter Coxhead
Author: Matthew Guille
Author: Graham J. Tizzard ORCID iD
Author: Simon J. Coles ORCID iD
Author: Helfrid Hochegger
Author: James E. Bradner
Author: James Spencer

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