A minimally-masked inactive prodrug of panobinostat that is bioorthogonally activated by gold chemistry

Belén Rubio-ruiz; Ana M. Pérez-lópez; Víctor Sebastián; Asier Unciti-broceta

doi:10.1016/j.bmc.2021.116217

A minimally-masked inactive prodrug of panobinostat that is bioorthogonally activated by gold chemistry

Belén Rubio-ruiz, Ana M. Pérez-lópez, Víctor Sebastián, Asier Unciti-broceta

Research output: Contribution to journal › Article › peer-review

Abstract

The recent incorporation of Au chemistry in the bioorthogonal toolbox has opened up new opportunities to deliver biologically independent reactions in living environments. Herein we report that the O-propargylation of the hydroxamate group of the potent HDAC inhibitor panobinostat leads to a vast reduction of its anticancer properties (>500-fold). We also show that this novel prodrug is converted back into panobinostat in the presence of Au catalysts in vitro and in cell culture

Original language	English
Pages (from-to)	116217
Journal	Bioorganic and Medicinal Chemistry
Early online date	15 May 2021
DOIs	https://doi.org/10.1016/j.bmc.2021.116217
Publication status	E-pub ahead of print - 15 May 2021

Keywords / Materials (for Non-textual outputs)

Bioorthogonal catalysis
gold nanoparticles
HDAC inhibitors
anticancer therapies

Access to Document

10.1016/j.bmc.2021.116217

A minimally-masked inactive prodrug of panobinostat that is bioorthogonally activated by gold chemistry_AAMAccepted author manuscript, 819 KB

https://linkinghub.elsevier.com/retrieve/pii/S096808962100225X

Locally-Controlled Activation of Chemotherapeutics by Palladium Catalysis as a Novel Anticancer Technology
Unciti-Broceta, A. (Principal Investigator) & Brennan, P. (Co-investigator)
EPSRC
1/04/16 → 30/09/21
Project: Research

Edinburgh Drug Discovery
Unciti-Broceta, A. (Manager), Webster, S. (Manager) & Carragher, N. (Manager)
Institute of Genetics and Cancer
Facility/equipment: Facility

Cite this

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title = "A minimally-masked inactive prodrug of panobinostat that is bioorthogonally activated by gold chemistry",

abstract = "The recent incorporation of Au chemistry in the bioorthogonal toolbox has opened up new opportunities to deliver biologically independent reactions in living environments. Herein we report that the O-propargylation of the hydroxamate group of the potent HDAC inhibitor panobinostat leads to a vast reduction of its anticancer properties (>500-fold). We also show that this novel prodrug is converted back into panobinostat in the presence of Au catalysts in vitro and in cell culture",

keywords = "Bioorthogonal catalysis, gold nanoparticles, HDAC inhibitors, anticancer therapies",

author = "Bel{\'e}n Rubio-ruiz and P{\'e}rez-l{\'o}pez, \{Ana M.\} and V{\'i}ctor Sebasti{\'a}n and Asier Unciti-broceta",

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doi = "10.1016/j.bmc.2021.116217",

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T1 - A minimally-masked inactive prodrug of panobinostat that is bioorthogonally activated by gold chemistry

AU - Rubio-ruiz, Belén

AU - Pérez-lópez, Ana M.

AU - Sebastián, Víctor

AU - Unciti-broceta, Asier

PY - 2021/5/15

Y1 - 2021/5/15

N2 - The recent incorporation of Au chemistry in the bioorthogonal toolbox has opened up new opportunities to deliver biologically independent reactions in living environments. Herein we report that the O-propargylation of the hydroxamate group of the potent HDAC inhibitor panobinostat leads to a vast reduction of its anticancer properties (>500-fold). We also show that this novel prodrug is converted back into panobinostat in the presence of Au catalysts in vitro and in cell culture

AB - The recent incorporation of Au chemistry in the bioorthogonal toolbox has opened up new opportunities to deliver biologically independent reactions in living environments. Herein we report that the O-propargylation of the hydroxamate group of the potent HDAC inhibitor panobinostat leads to a vast reduction of its anticancer properties (>500-fold). We also show that this novel prodrug is converted back into panobinostat in the presence of Au catalysts in vitro and in cell culture

KW - Bioorthogonal catalysis

KW - gold nanoparticles

KW - HDAC inhibitors

KW - anticancer therapies

U2 - 10.1016/j.bmc.2021.116217

DO - 10.1016/j.bmc.2021.116217

M3 - Article

SN - 0968-0896

SP - 116217

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

ER -

A minimally-masked inactive prodrug of panobinostat that is bioorthogonally activated by gold chemistry

Abstract

Keywords / Materials (for Non-textual outputs)

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Projects

Locally-Controlled Activation of Chemotherapeutics by Palladium Catalysis as a Novel Anticancer Technology

Equipment

Edinburgh Drug Discovery

Cite this