## 4 Conclusions  
In this study, 19 novel \(N^{\prime}\)-(4-/3-/2-/non-substituted benzylidene)-4-[(4-methylphenyl)] sulfonyl-oxy]benzohydrazide derivatives were synthesized, and compounds **3o** and **3s** were found to have the most potent inhibitory activity against MAO-A and MAO-B, respectively, with IC\({}_{50}\) values of 1.54 uM for **3o** towards MAO-A and 3.64 uM for **3s** towards _MAO-B_, and moderate selectivities. MAO-B inhibitory activity was increased in the order of 3-> 4-> 2-NO\({}_{2}\) groups in **3s**, **3t**, and **3r**, respectively. All compounds weakly inhibited AChE and BChE. However, **3e**, **3f**, and **3n** inhibited BACE-1 with IC\({}_{50}\) values of 8.63, 9.92, and 8.47 uM, respectively, with higher potencies than the reference compound quercetin. Compounds **3o** and **3s** were reversible and competitive inhibitors of MAO-A and MAO-B, respectively. It is concluded that **3o** and **3s** are effective MAO-A and MAO-B inhibitors, respectively, and **3e**, **3f**, and **3n** are effective BACE-1 inhibitors. These results suggest that these compounds can be considered potential agents for the treatment of AD. Computational studies shed light on the interactions of compounds **3e**, **3f**, and **3n** with BACE1 and those of **3s** and **3o** with MAOs, and these results agree with the experimental data. Compounds **3e**, **3f**, and **3n** can strongly interact with the S1 and S2 binding regions of the BACE-1 catalytic site through a set of both polar and hydrophobic interactions. For compounds **3o** and **3s**, the networks of aromatic interactions with FAD, Y407, and Y444 of MAO-A and FAD, Y398, and Y435 of MAO-B are crucial for binding at the MAO binding sites. Furthermore, dipole and \(\pi\)-\(\pi\) contacts with the F352 and Y326 residues of MAO-A and MAO-B, respectively, enhance the interaction with binding pockets and can thus explain the IC50 experimental data.  
The following is available online at [[http://www.mdpi.com/xxx/s1](http://www.mdpi.com/xxx/s1)]([http://www.mdpi.com/xxx/s1](http://www.mdpi.com/xxx/s1)). Figures S1-S76 for 1H-NMR, 13C-NMR, EST MS, and chromatogram data of the compounds.  
Conceptualization: H.E.S., I.S.D. and H.K.; synthesis: H.E.S., I.S.D., S.Y., A.B.A., A.K. and M.A.A.; biological activity: J.M.O. and G.S.J.; docking analysis: N.G. and O.N.; original draft writing: J.M.O., I.S.D., H.E.S. and B.M.; review and editing: H.K., I.S.D. and B.M.;  
\begin{table}
\begin{tabular}{c c c c c c c} \hline \hline  & **MW** & **logP** & **HBA** & **HBD** & **MR** & \
\begin{tabular}{c} **Human Oral** \\ **Absorption** \\ \end{tabular} &
\begin{tabular}{c} **Violation of** \\ **Lipinski’sRule of Five** \\ \end{tabular} \\ \hline
**3s** & 439.441 & 4.199 & 3 & 1 & 114.993 & 2 & 0 \\
**3o** & 412.434 & 4.510 & 3 & 1 & 107.885 & 3 & 0 \\
**3f** & 424.470 & 4.288 & 4 & 1 & 114.132 & 3 & 0 \\
**3e** & 424.470 & 4.288 & 4 & 1 & 114.132 & 3 & 0 \\
**3n** & 412.434 & 4.510 & 3 & 1 & 107.885 & 3 & 0 \\ \hline \hline \end{tabular}  
* MW—molecular weight; logP—the logarithm of the 1-octanol/water partition coefficient; HBA/HBD—the number of hydrogen bond acceptor/donor atoms; MR—molar refractivity; Human oral absorption, predicted qualitative human absorption (1, 2, or 3 indicate low, medium, and high amounts, respectively); [PERSON]’s rule of five, the number of violations (zero is optimal).  
\end{table}
Table 2: Physiochemical properties relevant to drug-likeness.  
supervision: H.K.; funding acquisition: H.K. and A.K. All authors have read and agreed to the published version of the manuscript.  
This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (NRF-2019R1A2C1088967), Republic of Korea, and by Scientific Research Projects Coordination Unit of Karadeniz Technical University (Project Number: FLO-2019-7883), Turkey.  
Not applicable.  
Authors acknowledge Taif University Researchers Supporting Project number (TURSF-2020/68), Taif University, Taif, Saudi Arabia.  
The authors declare no conflict of interest.