Abstract
To combat emerging antimicrobial-resistant microbes, there is an urgent need to develop new antimicrobials with better therapeutic profiles. For this, a series of 13 new spiropyrrolidine derivatives were designed, synthesized, characterized and evaluated for their in vitro antimicrobial, antioxidant and antidiabetic potential. Antimicrobial results revealed that the designed compounds displayed good activity against clinical isolated strains, with
5d
being the most potent (MIC 3.95 mM against
Staphylococcus aureus
ATCC 25923) compared to tetracycline (MIC 576.01 mM). The antioxidant activity was assessed by trapping DPPH, ABTS and FRAP assays. The results suggest remarkable antioxidant potential of all synthesized compounds, particularly
5c
, exhibiting the strongest activity with IC
50
of 3.26 ± 0.32 mM (DPPH), 7.03 ± 0.07 mM (ABTS) and 3.69 ± 0.72 mM (FRAP). Tested for their
α
-amylase inhibitory effect, the examined analogues display a variable degree of
α
-amylase activity with IC
50
ranging between 0.55 ± 0.38 mM and 2.19 ± 0.23 mM compared to acarbose (IC
50
1.19 ± 0.02 mM), with the most active compounds being
5d
, followed by
5c
and
5j
, affording IC
50
of 0.55 ± 0.38 mM, 0.92 ± 0.10 mM, and 0.95 ± 0.14 mM, respectively. Preliminary structure–activity relationships revealed the importance of such substituents in enhancing the activity. Furthermore, the ADME screening test was applied to optimize the physicochemical properties and determine their drug-like characteristics. Binding interactions and stability between ligands and active residues of the investigated enzymes were confirmed through molecular docking and dynamic simulation study. These findings provided guidance for further developing leading new spiropyrrolidine scaffolds with improved dual antimicrobial and antidiabetic activities.