Uric acid (UA) is an organic heterocyclic compound with molecular formula of C5H4N4O3. UA is biosynthesized in the liver and is a by-product of metabolism of purines, xanthine and other related compounds and is majorly excreted through urine and in few amounts through blood and other bodily fluids [1]. Discovery of UA is a little mystery as in 1776, Swedish chemist Carl Wilhelm Scheele was studying the chemistry of urine, so he dried the urine and treated it with nitric acid which led to precipitation of white crystalline substance [2]. This white substance was later identified by William Hyde Wollaston as UA in 1797 [3].

Chemically, UA is an oxopurine with three oxo groups at 2, 6 and 8 positions of the purine ring. Biologically, UA is a potent antioxidant which has abilities to act as an immune system stimulant and also helps in maintaining blood pressure in salt poor conditions [4]. Therefore, suggesting that normal UA levels are beneficial for human health. But overproduction of UA or hyperuricemia may lead to crystallisation of UA in the form of monosodium urate monohydrate microcrystals and these crystals start depositing in various parts of the body mainly in joints. This excessive deposition of UA in joints or other tissues may lead to development of Gout, metabolic syndrome, renal and cardiovascular diseases [5], [6]. Therefore, this makes it mandatory for us to manage and monitor UA levels in the blood; and as per European guidelines, Serum Uric acid (SUA) levels should be ≤6 mg/dL.

In the US about 14.6 % (estimated 32.5 million individuals) of the population was found to be affected by hyperuricemia and men (24.7 %) were found to be much more prevalent as compared with women (5.2 %) [7]. This number can reach a value of 78 million (26 %) US adults’ patients by 2040 [8]. In 2013, national arthritis-attributable medical costs were $140 billion which may increase with time and creating a burden on the government bodies [8]. This surge in cases builds up the need to search and develop potent drugs or targets which are cost-efficient. This surge in cases can also be a result of increased consumption junk food and sedentary lifestyle.

On studying the pathology of hyperuricemia, researcher found Xanthine oxidase (XO) enzyme to be involved in the overproduction of UA, as it catalyses the conversion of purine-based compounds to UA along with the generation of reactive oxidative species as shown in Fig. 1[9], [10]. So, over intake of purine-based foods or over activation of XO enzyme were found to be directly impacting the production of UA in the body. On behalf of these, patients are first put on non-pharmacological therapy which includes reducing purine, sugars and alcohol in diet; consuming a diet rich in vegetables and increasing water intake [11]. If this therapy fails to control the SUA levels, they are switched to pharmacological therapy which either work by reducing biosynthesis of UA by inhibiting XO enzyme (Uricostatic drugs, e.g., allopurinol, Febuxostat) or by increasing the excretion of urate (Uricosuric drugs, e.g., probenecid, benzbromarone) by blocking the URAT1 pathway [12]. On further investigation, it was found that uricosuric drugs are least preferred as they don’t alter the biosynthesis of UA via purine metabolism and are contraindicated in patients with renal impairment (e.g. nephrolithiasis). Therefore, Uricostatic drugs or XO inhibitors are used as first-line drugs to treat hyperuricemic patients [13].

XO is dimeric molybdoflavoprotein that catalyses the hydroxylation of hypoxanthine to xanthine and xanthine to UA along with generation of superoxide anion via purine scavenging pathway as shown in Fig. 1. Therefore, its inhibition will result in reduced production of UA in the body [14]. The active site of this enzyme comprises of 18 amino acids. Among them, Glu802, Arg880, Phe914, Phe1009 and Glu1261 are involved in catalytic activity of the enzyme [15]. Hence, to inhibit the catalytic activity of the enzyme, it’s mandatory for an inhibitor to interact with these amino acids and block the active site.