Spectroscopic investigations, ab-initio DFT calculations, molecular docking and in-vitro assay studies of novel oxovanadium(V)chalcone complexes as potential antidiabetic agents

A series of four novel oxovanadium(V)chalcone complexes ([VO(LI-IV)(2)(Cl)]; where HLI= 1-(2-Hydroxy-phenyl)-3-phenyl-propenone, HLII= 1-(1-Hydroxy-naphthalen-2-yl)-3-phenyl-propenone, HLIII = 1-(2-Amino-phenyl)-3-phenyl-propenone, HLIV = 4-Hydroxy-6-methyl-3-(3-phenyl-acryloyl)-pyran-2-one) were designed and synthesized by performing chemical reaction between VOCl(3 )and respective chalcone derivatives in 1:2 molar ratio. Their formation as well as chemical structures were confirmed by FTIR, UV-Visible, H-1-NMR, SEM, EDS, and mass spectrometry spectroscopic techniques. The geometry of the synthesized complexes was purposed to be octahedral on the basis of the characterization. Further computational and structural parameters of the synthesized complexes were determined in order to establish their thermodynamic stability/chemical reactivity of the synthesized complexes. Density Functional Theory (DFT) method was employed to calculate the molecular geometry and vibrational frequencies of the synthesized complexes using B3LYP hybrid functional at 6-31G * level of basis set. Further, Spartan'20 V1.0.0 program package was used to calculate the( 1)H-NMR spectra with (DFT/ B3LYP) in the gaseous phase to validate the structure of oxovanadium(V) complexes. The experimentally obtained results were found to be well correlated with theoretical results with a correlation value > 0.96. Global reactivity descriptors helps to explain the bioactivity of complexes hence, were calculated from the HOMO-LUMO energies. The enzymatic assay experiments indicated that all the four synthesized complexes have significant to moderate inhibition potential against alpha-glucosidase, and alpha-amylase enzymes. Among all the oxovanadium(V)chalcone complexes, complex 4 showed excellent and superior inhibition potency almost equivalent to the commercially available Acarbose drug and even better in case of alpha-amylase. The observed IC50 value of complex 4 for the inhibition of alpha-amylase and alpha-glucosidase was calculated to be 16.36 mu g/mL and 57.27 mu g/mL, respectively. The Kinetic parameters calculated from the Lineweaver-Burk plot showed that complex 4 were uncompetitive and mixed inhibitor of alpha-amylase and alpha-glucosidase respectively. Thereafter,the antiradical activity of synthesized vanadium(V)chalcone complexes was assessed with the help of DPPH radical scavenging assay. The results demonstrated that all the complexes were remarkable free radical scavengers for the DPPH. The complex 1 was observed to be best among them with the 0.03 mu g/mL IC(50 )value. The AutoDockTools-1.5.6 software was used to examine structure-activity relationship and the binding interactions between oxovanadium(V) complexes and protein target alpha-amylase, alpha-glucosidase, and Myeloperoxidase respectively. The in-vitro as well as in-silico biological activity studies showed significant and major improvements after complexation of chalcone derivatives with vanadium oxychloride (VOCl3). Thus, oxovanadium(V)chalcone complexes were found to be potent inhibitors of the alpha-glucosidase and alpha-amylase enzyme.(c) 2022 Elsevier B.V. All rights reserved.