Design, synthesis, crystal structures, computational studies, in vitro and in silico monoamine oxidase-A&B inhibitory activity of two novel S-benzyl dithiocarbamates

Abstract

Two novel trifluoromethyl containing S-benzyl dithiocarbamates (1-2) have been successfully synthesized and their structures were evaluated by means of 1H- and 13C-NMR spectroscopy, FT-IR spectroscopy, and single-crystal XRD analysis. Both S-benzyl dithiocarbamates, 1 and 2, differ between them by the position of the trifluoromethyl group in the aromatic ring. The great molecular similarity is reflected in similar crystal structures with similar intermolecular interactions. Interestingly, the low temperature used in the XRD analysis showed that compound 1 is constituted by three conformers while compound 2 shows two independent conformers in the asymmetric unit. Considering that each conformer is organized in independent molecular sheets, compound 1 has a longer c parameter compared to compound 2. The position of the trifluoromethyl group also has implications in the chemical behavior which is demonstrated in the HOMO-LUMO orbitals computed by the B3LYP method with 3–21G* basis set. Bioassay outcome displays that both compounds 1 and 2 exhibit excellent inhibition potential against monoamine oxidases (MAO-A and MAO-B) with p-CF3 S-benzyl dithiocarbamate 1 (IC50=16.02 ± 5.135 μg/mL, 1.284 ± 0.66 μg/mL) being more efficient than m-CF3 S-benzyl dithiocarbamate 2 (IC50=18.37± 4.030 µM, 3.164 ± 0.456 µM) against MAO-A and MAO-B, respectively. The results of binding energy values computed via docking studies showed a remarkable agreement with in-vitro results.