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Reactivity of the glutathione species towards the reduction of ormaplatin (or tetraplatin)

Dong, Jingran; Huo, Shuying; Shen, Shigang; Xu, Jianzhong; Shi, Tiesheng and Elding, Lars Ivar LU (2016) In Bioorganic and Medicinal Chemistry Letters 26(17). p.4261-4266
Abstract

The reduction of ormaplatin (tetraplatin), a prototype for Pt(IV) anticancer prodrugs, by glutathione (GSH) was kinetically characterized over a wide pH range at 25.0 °C and 1.0 M ionic strength. The reduction follows overall second-order kinetics, giving rise to the oxidized glutathione as the oxidation product, which was identified by high-resolution mass spectrometry. The reaction mechanism put forward involves parallel attacks by all the GSH species on the Pt(IV) prodrug as rate-determining steps. All rate constants for the rate-determining steps have been derived for the first time, enabling the construction of the reactivity of GSH species versus their pH distribution diagram. The diagram clearly displays that only one out of the... (More)

The reduction of ormaplatin (tetraplatin), a prototype for Pt(IV) anticancer prodrugs, by glutathione (GSH) was kinetically characterized over a wide pH range at 25.0 °C and 1.0 M ionic strength. The reduction follows overall second-order kinetics, giving rise to the oxidized glutathione as the oxidation product, which was identified by high-resolution mass spectrometry. The reaction mechanism put forward involves parallel attacks by all the GSH species on the Pt(IV) prodrug as rate-determining steps. All rate constants for the rate-determining steps have been derived for the first time, enabling the construction of the reactivity of GSH species versus their pH distribution diagram. The diagram clearly displays that only one out of the five GSH species is the mainly responsible for the reduction of ormaplatin at the physiological pH of 7.4.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Anticancer, Glutathione, Kinetic analysis, Ormaplatin , Reduction, Tetrapaltin
in
Bioorganic and Medicinal Chemistry Letters
volume
26
issue
17
pages
6 pages
publisher
Elsevier
external identifiers
  • scopus:84981316235
  • wos:000381959900019
ISSN
0960-894X
DOI
10.1016/j.bmcl.2016.07.046
language
English
LU publication?
yes
id
e7b7129e-5619-4377-b29c-e5bdeea64a40
date added to LUP
2016-11-28 13:42:28
date last changed
2017-08-06 05:14:10
@article{e7b7129e-5619-4377-b29c-e5bdeea64a40,
  abstract     = {<p>The reduction of ormaplatin (tetraplatin), a prototype for Pt(IV) anticancer prodrugs, by glutathione (GSH) was kinetically characterized over a wide pH range at 25.0 °C and 1.0 M ionic strength. The reduction follows overall second-order kinetics, giving rise to the oxidized glutathione as the oxidation product, which was identified by high-resolution mass spectrometry. The reaction mechanism put forward involves parallel attacks by all the GSH species on the Pt(IV) prodrug as rate-determining steps. All rate constants for the rate-determining steps have been derived for the first time, enabling the construction of the reactivity of GSH species versus their pH distribution diagram. The diagram clearly displays that only one out of the five GSH species is the mainly responsible for the reduction of ormaplatin at the physiological pH of 7.4.</p>},
  author       = {Dong, Jingran and Huo, Shuying and Shen, Shigang and Xu, Jianzhong and Shi, Tiesheng and Elding, Lars Ivar},
  issn         = {0960-894X},
  keyword      = {Anticancer,Glutathione,Kinetic analysis,Ormaplatin ,Reduction,Tetrapaltin},
  language     = {eng},
  month        = {09},
  number       = {17},
  pages        = {4261--4266},
  publisher    = {Elsevier},
  series       = {Bioorganic and Medicinal Chemistry Letters},
  title        = {Reactivity of the glutathione species towards the reduction of ormaplatin (or tetraplatin)},
  url          = {http://dx.doi.org/10.1016/j.bmcl.2016.07.046},
  volume       = {26},
  year         = {2016},
}