Exploring Probenecid Derived 1,3,4-Oxadiazole-Phthalimide Hybrid as α-Amylase Inhibitor: Synthesis, Structural Investigation, and Molecular Modeling

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 (H-1 and C-13) 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 pi center dot center dot center dot pi stacking interactions in PESMP. PESMP was found to have a high stability and lower reactivity in terms of global reactivity parameters. alpha-Amylase inhibition studies revealed that the PESMP was a good inhibitor of alpha-amylase with an s value of 10.60 +/- 0.16 mu g/mL compared with that of standard acarbose (IC50 = 8.80 +/- 0.21 mu g/mL). Molecular docking was also utilized to reveal the binding pose and features of PESMP against the alpha-amylase enzyme. Via docking computations, the high potency of PESMP and acarbose towards the alpha-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 alpha-amylase inhibitors.

Automated summary

In this study, a 1,3,4-oxadiazole-phthalimide hybrid compound was synthesized and characterized. It was found to have high stability and good inhibitory activity against alpha-amylase. Molecular docking simulations also revealed the binding features and high potency of the compound as an alpha-amylase inhibitor.