Synthesis and in-silico molecular modelling, DFT studies, antiradical and antihyperglycemic activity of novel vanadyl complexes based on chalcone derivatives

Abstract

Diabetes mellitus (DM) will be one of the ten most deadly diseases in the near future, according to a WHO survey. It is, therefore, of utmost importance to design and synthesize effective inhibitors to be used in the treatment of DM disease. In this respect, a new series of chalcone derivatives and their vanadyl complexes of composition [VO(LI-III)2]SO4 and [VO(LIV)2] (where LI=1-(2-Hydroxy-phenyl)-3-phenyl-propenone, LII=1-(1-Hydroxy-naphthalen-2-yl)-3-phenyl-propenone, LIII = 1-(2-Amino-phenyl)-3-phenyl-propenone, LIV = 4-Hydroxy-6-methyl-3-(3-phenyl-acryloyl)-pyran-2-one) were designed and synthesized in this work. Physioanalytical, FTIR, 1H NMR, 13C NMR, UV-Visible, EPR, SEM, EDX, and mass spectrometry data were used to establish their formation and validate their structures. After that, biological effects such as antiradical, α-glucosidase, and α-amylase inhibitory activities of synthesized vanadyl-chalcone complexes were assessed. Furthermore, the Density Functional Theory (DFT) studies with 6-31G*/B3LYP level were used to achieve optimal molecular geometries and HOMO-LUMO gap to analyze the chemical and kinetic stability of the complexes. Molecular docking studies were performed as well to investigate the interactions between the synthesized complexes and target enzyme viz. α-amylase and α-glucosidase. The in-vitro biological studies showed major and significant improvements upon the complexation of ligands. Complex 3 (for α-glucosidase) and complex 4 (for α-amylase), in particular, were found to have a remarkable ability to lower blood sugar levels. Otherwise, the potent α-glucosidase and α-amylase inhibitory activity was observed in all of the synthesized complexes. The complexes with the best IC50 values were studied further in terms of enzyme kinetics and displayed mixed inhibition with both enzymes. Furthermore, using the DPPH assay, the antiradical activity of chalcones and their vanadyl complexes was evaluated for their efficacy in releasing oxidative stress. From the obtained results, complex 3 and 4 exhibited remarkable antiradical activity.