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.
Keywords: Lichen, Roccella montagnei and Parmotrema cooperi, polyketide, methyl-β-orcinol carboxylate, urease inhibition,
STD-NMR spectroscopy, molecular docking.
Rights & PermissionsPrintExport