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Experimental, biophysical, and molecular modelling studies between 25I-NBOH and 25I-NBOMe with human serum albumin (HSA) have indicated that these recreational drugs simultaneously bind to site I and II of the protein, with 25I-NBOMe showing a greater affinity for the transport protein, and that both compounds were able to perturb the native structure of HSA. The 25I-NBOH and 25I-NBOMe drugs spontaneously interact with protein (ΔG < 0), and with the complex formation in the ground state (static quenching). Preferred forces in the interaction process were determined as hydrogen bonding and van der Waals forces. From 1H NMR studies, it was possible to determine the epitope of the molecules, as these and other results agree with the theoretical molecular docking. Overall, our results suggest that the interaction between 25I-NBOH and 25I-NBOMe with HSA can affect its distribution in the body and cause harmful effects, resulting from conformational changes in the protein which can affect its function from the decreased availability of HSA to carry other essential compounds.

Twenty-six Biginelli adducts were synthesized through an ionic liquid-assisted synthesis with up to 92% yield. Sixteen of these Biginelli adducts were then assayed to determine their antiureolytic activity against purified urease from jack beans. The substances BA7-S, BA9-S and BA11-S were shown to be as efficient inhibitors as hydroxyurea, a positive control used in in vitro screening assay against urease. Fluorescence studies revealed that BA7-S, BA9-S, BA11-S and BA5-S possessed high binding constant values of 5.95, 6.72, 4.55, and 4.28 M−1, respectively, while BAS12-S, without substituents, showed a low value of log Kb = 2.16 M−1. In addition, in the most thermodynamically favorable BA5-S and BA7-S urease complexes, the corresponding Biginelli adducts were capable of interacting with the active site of urease through non-ionic interactions, such as hydrophobic interactions, or hydrogen and van der Waals interactions, respectively. In silico studies also supported that the BAs interact with the active site, confirming the fluorescence and kinetic assay studies, which clearly indicate that BA5-S and BA7-S are competitive inhibitors (Ki = 0.96 and 0.57 mM, respectively). In silico studies also showed that the substituents in the aromatic ring interact with Ni atoms to form a stable complex.

The interaction of (S)-(−)-usnic acid (2) and fumarprotocetraric acid (3), isolated from Cladonia rappii (lichen), and commercial (R)-(+)-usnic acid (1) with urease was investigated in vitro by molecular spectroscopy at pH 7.4 and kinetics experiments using jack bean type III urease. All lichen compounds tested interact with urease by a statistical quenching mechanism forming non-fluorescent complexes that change the native protein structure. Formation of complexes was spontaneous and stabilized mainly by electrostatic forces, in which the interaction magnitude was determined to be 3 < 2 < 1. Compound 2, whose tridimensional structure is disclosed here, acts as a mixed inhibitor while compounds 1 and 3 function as competitive ones. The (R)-(+)-UA (1) is the most efficient lichen metabolite with respect to impairment of the growth of five H. pylori strains. The minimum inhibitory concentrations (MIC) for the lichen metabolites tested were lower (from 2- to 7.8-fold) than those of omeprazole (reference drug) against all H. pylori strains tested. Overall, the lichen metabolites 1–3 are promising lead compounds for the design of more efficient urease inhibitors for the treatment of H. pylori infections.