Exploring Probenecid Derived 1,3,4-Oxadiazole-Phthalimide Hybrid as α-Amylase Inhibitor: Synthesis, Structural...

Area of Science:

• Medicinal Chemistry
• Organic Synthesis
• Computational Chemistry

Background:

• The 1,3,4-oxadiazole scaffold is a key pharmacophore in biologically active molecules.
• Probenecid was utilized as a starting material for synthesizing novel compounds.

Purpose of the Study:

• To synthesize and characterize a novel 1,3,4-oxadiazole-phthalimide hybrid (PESMP).
• To evaluate the potential of PESMP as an alpha-amylase inhibitor.
• To elucidate the binding interactions of PESMP with alpha-amylase using computational methods.

Main Methods:

• Synthesis of PESMP from probenecid.
• Structural confirmation using NMR spectroscopy and single-crystal X-ray diffraction.
• Hirshfeld surface analysis and quantum mechanical computations.
• In vitro alpha-amylase inhibition assays.
• Molecular docking studies.

Main Results:

• PESMP was successfully synthesized in high yields and characterized.
• Hirshfeld analysis revealed the significance of pi-pi stacking interactions.
• PESMP exhibited high stability and low reactivity.
• PESMP showed potent alpha-amylase inhibition (IC50 = 10.60 ± 0.16 μg/mL), comparable to acarbose (IC50 = 8.80 ± 0.21 μg/mL).
• Molecular docking confirmed favorable binding interactions and potency for PESMP (-7.4 kcal/mol) and acarbose (-9.4 kcal/mol).

Conclusions:

• The synthesized PESMP compound is a promising alpha-amylase inhibitor.
• Structural and computational analyses provide insights into its inhibitory mechanism.
• PESMP represents a potential lead compound for developing new antidiabetic agents.