The dinitrobenzamide mustard prodrugs, PR-104A and SN27686, for use in a novel MNDEPT cancer prodrug therapy approach

Ball, Patrick, Thompson, Emma, Anderson, Simon, Gwenin, Vanessa, Ashoorzadeh, Amir, Smaill, Jeff and Gwenin, Chris ORCID: 0000-0003-0363-8168 (2023) The dinitrobenzamide mustard prodrugs, PR-104A and SN27686, for use in a novel MNDEPT cancer prodrug therapy approach. BIOSCIENCE REPORTS, 43 (4). BSR20230627-.

PDF
The dinitrobenzamide mustard prodrugs, PR-104A and SN27686, for use in a novel MNDEPT cancer prodrug therapy approach.pdf - Open Access published version
Download (1MB) | Preview

Official URL: http://dx.doi.org/10.1042/bsr20230627

Abstract

Directed enzyme prodrug therapy is a highly promising anti-cancer strategy. However, the current technology is limited by inefficient prodrug activation and the dose-limiting toxicity associated with the prodrugs being tested; to overcome these limitations, the dinitrobenzamide mustard prodrugs, PR-104A and SN27686, have been developed. The present study will assess both of these prodrugs for their potential uses in a novel magnetic-nanoparticle directed enzyme prodrug therapy strategy by determining their kinetic parameters, assessing the products formed during enzymatic reduction using HPLC and finally their ability to cause cell death in the ovarian cancer cell line, SK-OV-3. It was shown for the first time that the dinitrobenzamide mustard prodrugs are able to be reduced by the genetically modified nitroreductases, NfnB-cys and YfkO-cys, and that these enzyme/prodrug combinations can induce a significant cell death in the SK-OV-3 cell line, highlighting the potential for both enzyme/prodrug combinations for use in magnetic-nanoparticle directed enzyme prodrug therapy.

Item Type:	Article
Uncontrolled Keywords:	Humans, Neoplasms, Nitrogen Mustard Compounds, Antineoplastic Agents, Antineoplastic Agents, Alkylating, Prodrugs
Divisions:	Faculty of Science and Engineering > School of Physical Sciences
Depositing User:	Symplectic Admin
Date Deposited:	06 Jul 2023 08:22
Last Modified:	06 Jul 2023 08:22
DOI:	10.1042/BSR20230627
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3171447