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1,3,4-Oxadiazole moiety is a crucial pharmacophore in many biologically active compounds. In a typical synthesis, probenecid was subjected to a sequence of reactions to obtain a 1,3,4-oxadiazole–phthalimide hybrid (PESMP) in high yields. The NMR (1H and 13C) spectroscopic analysis initially confirmed the structure of PESMP. Further spectral aspects were validated based on a single-crystal XRD analysis. Experimental findings were confirmed afterwards by executing a Hirshfeld surface (HS) analysis and quantum mechanical computations. The HS analysis showed the role of the π⋯π stacking interactions in PESMP. PESMP was found to have a high stability and lower reactivity in terms of global reactivity parameters. α-Amylase inhibition studies revealed that the PESMP was a good inhibitor of α-amylase with an s value of 10.60 ± 0.16 μg/mL compared with that of standard acarbose (IC50 = 8.80 ± 0.21 μg/mL). Molecular docking was also utilized to reveal the binding pose and features of PESMP against the α-amylase enzyme. Via docking computations, the high potency of PESMP and acarbose towards the α-amylase enzyme was unveiled and confirmed by docking scores of −7.4 and −9.4 kcal/mol, respectively. These findings shine a new light on the potential of PESMP compounds as α-amylase inhibitors. [ABSTRACT FROM AUTHOR]

Sulphonamide and 1,3,4-oxadiazole moieties are present as integral structural parts of many drugs and pharmaceuticals. Taking into account the significance of these moieties, we herein present the synthesis, single-crystal X-ray analysis, DFT studies, and α-amylase inhibition of probenecid derived two S-alkylphtha-limide-oxadiazole-benzenesulfonamide hybrids. The synthesis has been accomplished in high yields. The final structures of both hybrids have been established completely with the help of different spectro-analytical techniques, including NMR, FTIR, HR-MS, and single-crystal X-ray diffraction analyses. In an effort to confirm the experimental findings, versatile quantum mechanical calculations and Hirshfeld Surface analysis have been performed. α-Amylase inhibition assay has been executed to investigate the enzyme inhibitory potential of both hybrids. The low IC50 value (76.92 ±0.19 µg/mL) of hybrid 2 shows the good α-amylase inhibition potential of the respective compound. Ultimately, the binding affinities and features of the two hybrids are elucidated utilising a molecular docking technique against the α-amylase enzyme. [ABSTRACT FROM AUTHOR]

• Novel trifluoromethyl containing S-benzyl dithiocarbamates have been synthesized. • Crystallographic, Hirshfeld surface, FMO energy analyses were conducted. • Compounds showed good inhibition towards monoamine oxidases-A&B. • Docking studies showed a high binding affinity for both monoamine oxidases. 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 -CF 3 S-benzyl dithiocarbamate 1 (IC 50 =16.02 ± 5.135 μg/mL, 1.284 ± 0.66 μg/mL) being more efficient than m -CF 3 S-benzyl dithiocarbamate 2 (IC 50 =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. [Display omitted] [ABSTRACT FROM AUTHOR]