A potential therapeutic agent for the treatment of hyperuricemia and gout: 3,4-Dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide

Eur J Pharm Sci. 2024 Apr 21:106778. doi: 10.1016/j.ejps.2024.106778. Online ahead of print.ABSTRACTUric acid, the metabolic product of purines, relies on xanthine oxidase (XOD) for production. XOD is a target for the development of drugs for hyperuricemia (HUA) and gout. Currently, treatment options remain limited for gout patients. 3, 4-Dihydroxy-5-nitrobenzaldehyde (DHNB) is a derivative of the natural product protocatechualdehyde with good biological activity. In this work, we identify a DHNB thiosemicarbazide class of compounds that targets XOD. 3,4-Dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazone can effectively inhibit XOD activity (IC50 value: 0.0437 μM) and exhibits a mixed inhibitory effect. In a mouse model of acute hyperuricemia, a moderate dose (10 mg/kg.w) of 3,4-dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide effectively controlled the serum uric acid content and significantly inhibited serum XOD activity. In addition, 3,4-Dihydroxy-5-nitrobenzaldehyde phenylthiosemicarbazide showed favorable safety profiles, and mice treated with the target compound did not show any symptoms of general toxicity following a single dose of 500 mg/kg. In the allopurinol group, 50% of the mice died. These results provide a structural framework and mechanism of XOD inhibition that may facilitate the design of hyperuricemia and gout treatments.PMID:38653341 | DOI:10.1016/j.ejps.2024.106778
Source: European Journal of Pharmaceutical Sciences - Category: Drugs & Pharmacology Authors: Source Type: research