Synthesis, Spectral Investigations, Biological Studies, and In Silico Approach of Vanillin Heterocyclic Acetamides

Objective: A sequence of biologically active vanillin acetamides bearing heterocyclic moiety (VHAs) specifically vanillin isoniazid acetamide (VISO), vanillin - 2 - pyridine acetamide (V2PR), vanillin - 4 - pyridine acetamide (V4PR), and vanillin - 2 - pyrimidine acetamide (V2PM) are synthesized and methodically characterized by spectroscopic techniques such as Nuclear Magnetic Resonance ( 1 H and 13 C NMR), Electrospray Ionization Mass, Fourier Transform Infrared and Ultraviolet-Visible spectroscopy. Further, the VHAs are inspected for in vitro biological activities such as anti-inflammatory by protein anti-denaturation, antidiabetic by enzyme inhibition method and the in vitro results are linked with the reference drug. Methods: To the acetonitrile solution of intermediate TBTU and trimethylamine is added at room temperature. The reaction mixture is stirred for 30 min and then the corresponding amine is added. The reaction mixture is stirred for 4 h and the reaction mixture is extracted with ethyl acetate. The evaporation of the solvent yielded the VHAs. The anti - inflammatory activity of VHAs is tested disbursing the Bovine serum albumin denaturation technique. The antidiabetic activity of VHAs is tested using the α-amylase inhibition method. Results and Discussion: The designed VHAs were successfully synthesized, well characterized by necessary spectroscopic techniques ( 1 H and 13 C NMR), Electrospray Ionization Mass and the structure of the VHAs was very clearly interpreted and discussed. The chemical structure and electronic topographies of VHAs agree with the biological activity distinctions. Hence, thorough analysis has been achieved in the computational methods such as Frontier molecular orbitals, molecular electrostatic potential and Mulliken charge distribution studies using the density functional theory method. The correlation between in vitro studies and docking results revealed that structural and electronic properties production an important role in biological activity. Conclusions: The VHAs obtainable very well α-amylase inhibitory activity and comparable results were obtained in the molecular docking studies.