Public Health Action
December 2023
Setting: The diagnosis of Buruli ulcer (BU) is frequently made by experienced health workers in rural regions. This leads to long turnaround times to confirm the diagnosis as it requires specialised laboratory infrastructure to perform confirmatory testing.
Background: Given the lack of success with protein antigens to detect BU in human sera, the aim of this study was to evaluate a range of single synthetic lipid antigens using an enzyme-linked immunosorbent assay (ELISA).
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.
View Article and Find Full Text PDFThe bacterial nitroreductase NfnB has been the focus of a great deal of research for its use in directed enzyme prodrug therapy in combination with the nitroreductase prodrug CB1954 with this combination of enzyme and prodrug even entering clinical trials. Despite some promising results, there are major limitations to this research, such as the fact that the lowest reported Km for this enzyme far exceeds the maximum dosage of CB1954. Due to these limitations, new enzymes are now being investigated for their potential use in directed enzyme prodrug therapy.
View Article and Find Full Text PDFDirected enzyme prodrug therapy (DEPT) is a cancer chemotherapy strategy in which bacterial enzymes are delivered to a cancer site before prodrug administration, resulting in prodrug activation at the cancer site and more localized treatment. A major limitation to DEPT is the poor effectiveness of the most studied enzyme for the CB1954 prodrug, NfnB from Escherichia coli, at concentrations suitable for human use. Much research into finding alternative enzymes to NfnB has resulted in the identification of the Xenobiotic reductases, XenA and XenB, which have been shown in the literature to reduce environmentally polluting nitro-compounds.
View Article and Find Full Text PDFDirected enzyme prodrug therapy (DEPT) involves the delivery of a prodrug-activating enzyme to a solid tumour site, followed by the subsequent activation of an administered prodrug. One of the most studied enzyme-prodrug combinations is the nitroreductase from (NfnB) with the prodrug CB1954 [5-(aziridin-1-yl)-2,4-dinitro-benzamide]. One of the major issues faced by DEPT is the ability to successfully internalize the enzyme into the target cells.
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