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New S-alkyl phthalimide 5a–f and S-benzyl 6a–d analogs of 5-(2-phenylquinolin-4-yl)-1,3,4-oxadiazole-2-thiol (4) were prepared by reacting 4 with N-bromoalkylphthalimide and CF3-substituted benzyl bromides in excellent yields. Spectroscopic techniques were employed to elucidate the structures of the synthesized molecules. The inhibition activity of newly synthesized molecules toward MAO-A, MAO-B, and AChE enzymes, was also assessed. All these compounds showed activity in the submicromolar range against all enzymes. Compounds 5a and 5f were found to be the most potent compounds against MAO-A (IC50 = 0.91 ± 0.15 nM) and MAO-B (IC50 = 0.84 ± 0.06 nM), while compound 5c showed the most efficient acetylcholinesterase inhibition (IC50 = 1.02± 0.65 μM). Docking predictions disclosed the docking poses of the synthesized molecules with all enzymes and demonstrated the outstanding potency of compounds 5a, 5f, and 5c (docking scores = −11.6, −15.3, and −14.0 kcal/mol against MAO-A, MAO-B, and AChE, respectively). These newly synthesized analogs act as up-and-coming candidates for the creation of safer curative use against Alzheimer's illness. [ABSTRACT FROM AUTHOR]

• Synthesis of S-benzyl dithiocarbamates derivatives via a single pot reaction setup. • Characterization of synthesized derivatives via NMR (1H and 13C), FT-IR and high resolution mass spectrometry. • In vitro enzyme inhibition assays against cholinesterase enzyme and monoamine oxidase. • Comprehensive in-silico investigations of synthesized derivatives. The current study was aimed to identify the selective and multi-targeted inhibitors of cholinesterase and monoamine oxidase enzymes. For this purpose, a novel class of multi-targeted compounds i.e., S -benzyl dithiocarbamates (1-30) was synthesized via a single pot reaction and the structures were characterized via NMR (1H and 13C), FT-IR and high-resolution mass spectrometry (HRMS). Moreover, the purity of the final products was determined using thin-layer chromatography (TLC). The compounds were evaluated for their inhibitory potential against cholinesterases (ChE) and monoamine oxidases (MAO). Among all derivatives, compound 5 (2-(trifluoromethyl) benzyl azepane-1-carbodithioate) depicted the maximum inhibition of AChE and BChE enzyme with an IC 50 value of 4.37±0.94 and 14.9±1.11, respectively. The derivative 11, expressed maximum inhibition of MAO-A and MAO-B with an IC 50 value of 1.14±0.03 and 1.01 ± 0.16 µM, respectively. Whereas, compound 16 exhibited maximum inhibitory potential against all four targeted enzymes i.e., AChE, BChE, MAO-A and MAO-B with an IC 50 value of 1.39±0.07 µg/ mL, 1.52±0.14 µg/ mL, 44.9±1.54 µM and 2.85±0.21 µM, respectively. The chemical reactivity profile of the potent derivatives were evaluated through density functional theory studies (DFT) where it was found that compound 5, 6 and 11 possessed reactive character due to narrow LUMO/HOMO energy gap. In addition, Molecular docking studies revealed excellent docking scores and produced sable protein-ligand complexes. The stability of protein-ligand complex was affirmed by molecular dynamic simulations which revealed stable and equilibrated trajectories of simulated complexes. The findings of in-vitro and in-silico studies suggested compound 16 as a promising multi-targeted compound that can be act as lead molecule for the treatment of AD. [Display omitted] [ABSTRACT FROM AUTHOR]