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In our pursuit of developing effective inhibitors for the enzymes α-amylase and α-glucosidase, which play a crucial role in carbohydrate metabolism related to type-2 diabetes, we synthesized compounds featuring a pyrrolidine ring. The synthesis involved coupling N-Boc-proline with various aromatic amines, resulting in the formation of distinct N-Boc proline amides. To investigate the influence of the Boc group on enzyme inhibition, the Boc group was subsequently removed. In vitro, testing against α-amylase and α-glucosidase, with metformin and acarbose as reference standards, revealed that the 4-methoxy analogue 3g showed noteworthy inhibitory activity, with IC50 values of 26.24 and 18.04 μg/mL, respectively. Compounds 3a with an IC50 value of 36.32 μg/mL and 3f with an IC50 value of 27.51 μg/mL displayed significant inhibitory activity against α-amylase and α-glucosidase, respectively. The results of molecular docking studies of the most potent pyrrolidine derivatives 3a and 3g with α-amylase and 3f and 3g with α-glucosidase showed good agreement with experimental data. Moreover, compound 3g showed strong binding interactions with HSA having binding constant values of 7.08 × 105 M−1 and 4.77 × 105 M−1 using UV–visible and fluorescence spectrophotometry, respectively.

Copper(II) acetate reacted with 2,3-isatin bisthiosemicarbazone (2,3 H2bitsc), 2,3-isatin bis-N1-methyl thiosemicarbazone (2,3 H2bitsc-N1-Me) and 2,3-isatin N1-phenyl thiosemicarbazone (2,3 H2bitsc-N1-Ph) in 1:1 (M: L) to form complexes of formula, [Cu(L)] (L = 2,3 bitsc 1, 2,3 bitsc-N1-Me 2, 2,3 bitsc-N1-Ph 3). The formation of bisthiosemicarbazone ligands and their complexes are supported by elemental analysis, FTIR, NMR (1H and 13C), ESR, and Mass. For complexes 1–3, two g values obtained are: g‖ = 2.24 (1), 2.17 (2), 2.26 (3) and g⊥ = 2.09 (1), 2.11 (2), 2.08 (3) which confirm axial symmetry. The square planar geometry is confirmed from higher g‖ values than g⊥ and presence g value of free electron in dx2-y2 ground term. Ligand to metal binding ratio of 1:1 is confirmed using UV–visible spectroscopy. The ligands (2,3 H2bitsc, 2,3 H2bitsc-N1-Me and 2,3 H2bitsc-N1-Ph) and complexes (1–3) were assessed for anti-tubercular (M. tuberculosis H37RV strain ATCC27294) and antibacterial (against E. coli and S. aureus) activities. The anti- tuberculosis activity of ligands (50 µg/mL-2,3 H2bitsc, 100 µg/mL-2,3 H2bitsc-N1-Me and H2bitsc-N1-Ph) gets enhanced on complexation with copper (25 µg /mL-1, 50 µg/mL 2 and 3). The minimal binding energies calculated through molecular modeling with mycobacterium tuberculosis enoyl reductase (PDB ID: 2H7M) is −7.6 (2,3 H2bitsc), −7.3 (2,3 H2bitsc-N1-Me), −9.6 (2,3 H2bitsc-N1-Ph), −8.7 (1), −8.9 (2), and −10.7 (3) Kcal/mol. Higher negative binding energy indicates more stabilized structure in the docked state for 1–3 which supports the experimental data. The drug-protein binding study with human serum albumin (HSA) was used to explore effective transport of molecules to their target sites in 2,3 H2bitsc and its complex 1. A high binding constant of complex 1 (6.09 × 105 M−1) with respect to the ligand 2,3 H2bitsc (4.90 × 105 M−1) indicates its strong binding affinities with HSA.