Gout is a chronic, inflammatory condition due to slow urate metabolism. The xanthine oxidase inhibitors, such as allopurinol and febuxostat, are recommended to reduce the uric acid level and prevent gout to attack in adult patients.1 Febuxostat can be considered as an alternative for patients with allopurinol hypersensitivity and renal impariment.2 Patients suffering from chronic gout are faced with costly medications––5.4$/80mgper/day––and the treatment can have an adverse effect on liver function.3 The emerging new generation of xanthine inhibitor, FYX051, displays a high cost effectiveness compared with febuxostat therapy in chronic gout patients.4 However, it is still expensive as estimated price of 18$/8mg per-day. Therefore, it is desirable to design new inhibitors with similar efficacy. Here, we computationally designed several modified inhibitors with 1,2,4-triazole ring being replaced by furan, thiophene, pyrrole, pyrazole, which could be synthesized in three steps. The binding energy between new inhibitors and substrate binding pocket at the active site of xanthine oxidase is also calculated. In addition, the new designed inhibitors will also help to probe the protonation state of glutamate 802, which is proposed to contribute the energy stabilization of inhibitors by hydrogen bonding.

Computational designed new inhibitors of xanthine oxidase for treatment of gout

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.