## 3 Results and Discussion
### Molecular Docking  
In order to investigate the binding mode of compounds **3e**, **3f**, and **3n** towards BACE-1 and **3o** and **3s** towards MAO-A and MAO-B, molecular docking analyses were performed.  
As shown in Figure 4, the binding modes of the three compounds demonstrate that the sulfone moiety and the carbonyl group are crucial for establishing a network of hydrogen bonds with both the main and side chains of T232 (at a distance of 2.2 A, 2.3 A and 2.5 A for **3e**, **3f** and **3n**) and the side chain of S325 (at a distance of 2.2 A, 2.2 A and 2.1 A for **3e**, **3f** and **3n**, respectively) in the S2 pocket. Furthermore, the 2-methoxy-benzyl moiety and the 2-fluorine benzyl moiety of compounds **3e** and **3n**, respectively, are involved in \(\pi\)-\(\pi\) interactions with Y71 at the S1 pocket. The docking scores were \(-\)5.59, \(-\)5.90, and \(-\)6.88 kcal/mol for **3e**, **3f**, and **3n**, respectively.  
Figure 3: Lineweaver-Burk plots for the inhibition of MAO-A by **3o** (**A**) and MAO-B by **3s** (**C**) and their respective secondary plots (**B**,**D**) of the slopes vs. inhibitor concentrations.  
As indicated in Figure 5, the para-methyl phenyl ring of compound **3o** is trapped in the aromatic cage formed by FAD, Y407, and Y444 of MAO-A and FAD, Y398, and Y435 residues of MAO-B. In addition, compound **3o** can establish \(\pi\)-stacking and T-shape \(\pi\)-\(\pi\) contacts with Y407 and F352 of MAO-A, respectively. For MAO-B, \(\pi\)-stacking and T-shape \(\pi\)-\(\pi\) interactions were detected with Y398 and Y326, a MAO-B selective residue. The docking scores were \(-9.73\) and \(-9.89\) kcal/mol in simulations of MAO-A and MAO-B, respectively.  
As shown in Figure 6, the para-methyl ring of compound **3s** interacts with the network of aromatic rings of FAD, Y398 and Y435 of MAO-B. Specifically, compound **3s** forms \(\pi\)-stacking and T-shape \(\pi\)-\(\pi\) interactions with the Y398 and Y326 of MAO-B. On the other hand, the binding pose of **3s** within MAO-A binding pocket resulted to be inverted. Its 3-NO\({}_{2}\).benzyl ring was partially trapped in the aromatic cage made of Y407, Y444, and FAD, but stabilized due to the presence of a dipole interaction with F352 residue. The docking scores were \(-5.67\) and \(-9.88\) kcal/mol for MAO-A and MAO-B, respectively.  
Figure 4: Catalytic site of BACE-1 in complex with compounds **3o** (**a**), **3f** (**b**), and **3n** (**c**), depicted as green, yellow, and blue sticks, respectively. Hydrogen bonds and \(\pi\)-\(\pi\) interactions are indicated by red arrows and green lines, respectively.  
Figure 5: Panels (**a**,**b**) show the catalytic sites of MAO-A and MAO-B, respectively, in complex with compound **3o**, depicted as green sticks. The \(\pi\)-\(\pi\) interactions are indicated by green lines.  
Figure 6: Panels (**a**,**b**) show the catalytic sites of MAO-A and MAO-B, respectively, in complex with compound **3s**, depicted as yellow sticks. The \(\pi\)-\(\pi\) and dipole interactions are indicated by green and blue lines, respectively.  
For the sake of completeness, all the interactions observed in docking simulations were automatically flagged by GLIDE software, for which the default distance thresholds are equal to 2.8 A for hydrogen bonds, and to 4.5 A and 5.5 A for \(\pi\)-stacking and T-shape contacts, respectively.