Flavonoids as Natural Inhibitors of Jack Bean Urease Enzyme

Enzyme urease plays an important role in several pathologies, such as urolithiasis, urinary catheter encrustation, hepatic encephalopathy, peptic ulcers, and gastric cancers. Its inhibition, therefore, has a major therapeutic significance. For this purpose, nine natural flavonoids 1-9 were evaluated for their urease inhibitory activity. Five of them (i.e. 1, 3, 7, 8, and 9) showed a urease inhibitory activity with IC50 values between 14.2 – 132.9 μM. Compounds 3, 8, and 9 showed a potent activity (IC50 =19.4 ± 1.39, 14.2 ± 0.30 and 17.7 ± 0.23 μM, respectively), in comparison to the standard urease inhibitor, acetohydroxamic acid (IC50 = 41.5 ± 1.50 μM). Furthermore, compounds 1, 7, and 9 exhibited a competitive mode of inhibition. Compounds 1, 3, 7, 8 and 9 were finally tested for cytotoxicity by using mouse fibroblast cell line (3T3 cell line) assay. Compounds 1, 3 and 7 were found non-cytotoxic, while compounds 8 and 9 showed some level of toxicity (IC50 = 18.75 ± 0.45 and 13.01 ± 0.70 μM, respectively). Present study identifies flavonoid 8 as a lead for further investigation towards designing novel urease inhibitors for the treatment of diseases associated with ureolytic bacteria.