Abstract

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.

Keywords: Flavonoids, peptic ulcer, urease inhibition, urolithiasis, mechanistic studies, cytotoxicity.

Graphical Abstract