In Vitro Competitive Inhibition by N-benzyl-N-(2-{2-oxo-2H,3H-[1,3]oxazolo[4,5-b]pyridin-3-yl}ethyl)methanesulfonamide Targeting Urate Oxidase (UOX) on Aspergillus flavus
Abstract
Worldwide there is a need for innovative approaches for reducing the growth of toxigenic fungi such as the Aspergillus genus. Food and grain spoilage due to this fungal infestation, and its toxic metabolites, Aflatoxin, link to liver disease and immunosuppression, are global economic and health issues. The development of a pre-harvest solution to infection by Aspergillus flavus would be more cost efficient and reduce the large health impact that aflatoxin infection linked disease causes. Prior study has shown purine metabolism is a recognized potential target for new antifungal drugs. However, there is limited research related to Aspergillus flavus and its purine degrading enzymes. There is also a need to uncover the consequences of an underperforming urate oxidase (UOX) in A. flavus as this information is necessary in the identification of high performing drugs. The objective of this research project was to determine the efficacy of ZINC000170611130 inhibiting the growth of Aspergillus flavus by targeting the UOX enzyme. This project built upon a hypothesis based on in silico binding simulation by using an in vitro disc diffusion test. The test drug did not significantly inhibit the growth of A. flavus which indicates that further research is needed to classify targets for the A. flavus uricase.
Keywords: aflatoxin, purine degradation, aspergillus flavus, urate oxidase