Natural urease inhibitors from Aloe vera resin and Lycium shawii and their structural-activity relationship and molecular docking study.

Bio-assay guided fractionation of the methanolic extract of Aloe vera resin and Lycium shawii stem successively afforded twenty three compounds; fourteen (1-14) from A. vera and nine (15-23) from L. shawii. All these compounds were characterized by 1D and 2D NMR spectroscopic techniques viz., H, C, DEPT, HSQC, HMBC, and COSY, and NEOSY, ESI-MS and compared with the reported literature. These compounds were assessed for their potential as urease inhibitors targeted in peptic ulcer. Among crude extracts and fractions of A. vera resin, n-butanol fraction (23.5 ± 1.7 μg·mL) showed the most potent urease inhibition followed by methanol (30.9 ± 0.3 μg/mL) and ethyl acetate (31.7 ± 0.5 μg·mL). In case of L. shawii, ethyl acetate fraction exhibited the highest urease activity (41.0 ± 1.4 μg/mL) trailed by dichloromethane (55.2 ± 1.5 μg/mL) fraction. Among the isolates, compounds 7, 11 and 23 were found to be excellent urease inhibitors with IC values of 14.5 ± 0.90 µM, (16.7 ± 0.16 µM) and 14.0 ± 0.8 µM, respectively. To the best of our knowledge, this is the first report on the urease enzyme inhibitory activity of the said compounds excluding compound 18. In addition, the urease activity of different fractions of L. shawii stem was also reported for the first time. The molecular docking studies showed that all the active compounds well accommodate in the active site of the urease enzyme by interacting with key amino acids.