Chalcones: As Potent α-amylase Enzyme Inhibitors; Synthesis, In Vitro, and In Silico Studies

Abstract

Background: The inhibition of α-amylase enzyme is one of the best therapeutic approach for the management of type II diabetes mellitus. Chalcone possesses a wide range of biological activities.

Objective: In the current study chalcone derivatives (1-16) were synthesized and evaluated their inhibitory potential against α-amylase enzyme.

Methods: For that purpose, a library of substituted (E)-1-(naphthalene-2-yl)-3-phenylprop-2-en-1-ones was synthesized by Claisen-Schmidt condensation reaction of 2-acetonaphthanone and substituted aryl benzaldehyde in the presence of base and characterized via different spectroscopic techniques such as EI-MS, HRESI-MS, ¹H-, and ¹³C-NMR.

Results: Sixteen synthetic chalcones were evaluated for in vitro porcine pancreatic α-amylase inhibition. All the chalcones demonstrated good inhibitory activities in the range of IC₅₀ = 1.25 ± 1.05 to 2.40 ± 0.09 μM as compared to the standard commercial drug acarbose (IC₅₀ = 1.34 ± 0.3 μM).

Conclusion: Chalcone derivatives (1-16) were synthesized, characterized, and evaluated for their α- amylase inhibition. SAR revealed that electron donating groups in the phenyl ring have more influence on enzyme inhibition. However, to insight the participation of different substituents in the chalcones on the binding interactions with the α-amylase enzyme, in silico (computer simulation) molecular modeling analyses were carried out.

Keywords: Chalcones; diabetes mellitus; in vitro; molecular docking.; synthesis; α-amylase enzyme inhibition.