Close menu

SURE

Sunderland Repository records the research produced by the University of Sunderland including practice-based research and theses.

The Role and Inhibition of Reactive Oxygen Species (ROS) in Psoriasis

Todd, Adam (2009) The Role and Inhibition of Reactive Oxygen Species (ROS) in Psoriasis. Doctoral thesis, University of Sunderland.

Item Type: Thesis (Doctoral)

Abstract

Psoriasis is a chronic inflammatory skin disorder that affects around two percent
of the population. There are many treatments available for the management of
psoriasis including topical therapy, systemic agents and phototherapy. Despite
the number of treatments available, however, there are still problems in the
management of psoriasis.
It is suggested here that the thioredoxin enzyme system may play a role in the
pathology of psoriasis. Using specific molecular modelling techniques, a lead
compound, RDP00060, was identified as a potential inhibitor of thioredoxin
reductase, a key enzyme in the thioredoxin system. In vitro RDP00060 showed
moderate inhibitory activity against the thioredoxin enzyme system with an IC50
value of 1.4 mM. RDP00060 also showed powerful activity in an MTT assay
using a human papilloma virus immortalized keratinocyte (HPV-16) cell line.
To increase the inhibitory activity towards thioredoxin reductase, molecular
modelling techniques were used to identify analogues of RDP00060 with a high
binding affinity for thioredoxin reductase. Several novel compounds were then
synthesized, characterized and evaluated for inhibitory activity towards the
thioredoxin system. One of the compounds, N-(3,4-bis-(toluene-4-
sulfonylamino)phenyl)-2-furamide (33f) showed good inhibitory activity against
the thioredoxin enzyme with an IC50 value of 37 μM. It is anticipated that N-(3,4-
bis-(toluene-4-sulfonylamino)phenyl)-2-furamide (33f) binds to thioredoxin
reductase irreversibly through a 1,4-conjugate addition mechanism. This
compound also showed powerful activity in the MTT assay using an HPV-16
immortalized keratinocyte cell line.
Further testing revealed that N-(3,4-bis-(toluene-4-sulfonylamino)phenyl)-2-
furamide (33f) also showed apoptotic and antiproliferative properties in human Tcells.
As a result of this work, N-(3,4-bis-(toluene-4-sulfonylamino)phenyl)-2-
furamide (33f) has been selected for further investigation as a potential antipsoriatic
agent.

Full text not available from this repository.

More Information

Depositing User: Barry Hall

Identifiers

Item ID: 3699
URI: http://sure.sunderland.ac.uk/id/eprint/3699

Users with ORCIDS

Catalogue record

Date Deposited: 27 Mar 2013 11:35
Last Modified: 03 Feb 2015 13:25

Contributors

Author: Adam Todd

University Divisions

Collections > Theses

Subjects

Sciences > Pharmacy and Pharmacology

Actions (login required)

View Item (Repository Staff Only) View Item (Repository Staff Only)