Study of Binding Epitopes by STD-NMR Spectroscopy and Molecular Docking of Urease Inhibitors from Lichens

Lichen polyketides (1−14), isolated from Roccella montagnei and Parmotrema cooperi,were evaluated for their urease inhibitory potential. Compound 5 (methyl-β-orcinol carboxylate) was found to be the most potent inhibitor among the series with the IC50 = 17.4 ± 3.0 μM, as compared to the standard thiourea (IC50= 21.0±0.1 μM). SAR studies revealed that mononuclear polyketidesare more potent inhibitors as compared to depsides, diphenylethers, and dibenzofurans. Saturation transfer difference (STD) NMR experiments were used to identify the structural features responsible for the inhibition of urease enzyme at the atomic levels. STD-NMR technique revealed that aromatic moiety and methyl protons of the compound 5 are involved in interactions with the receptor protein. Since C-8 and C-10 methyl protons received the maximum saturation from the receptor protein, this indicated their close proximity to the protein. Weak STDNMR signals for lecanoric acid (8) could be attributed to its larger size. Molecular docking studies predicted that carboxylic moieties of these polyketides act as anchors to bind with the bimetallic active site of the urease enzyme.