Synthesis, characterization and antidiabetic studies of novel amantadine-derived Schiff base (AHB) and its Zn(ii), Co(ii), Cr(iii) and VO(iv) complexes

Abstract

Diabetes mellitus is a significant health issue in Pakistan, with rising prevalence rates posing serious challenges to public health. To tackle this issue, several strategies have been developed recently, among which the controlled conversion of dietary carbohydrates into glucose by inhibition of enzymes is an appropriate strategy. For this purpose, many synthetic drugs have been tried and explored. In this scenario, a new Schiff base ligand, (E)-2-((adamantan-2-ylimino)methyl)-6-bromo-4-chlorophenol (AHB), has been synthesized by a reflux reaction of amantadine with 3-bromo-5-chloro-2-hydroxybenzaldehyde. The transition metal complexes, [Cr(AHB)₃], [Zn(AHB)₂], [Co(AHB)₂], and [VO(AHB)₂], were also synthesized by reacting AHB with the respective metal salts. Structural elucidation of the prepared compounds was performed comprehensively by various physicochemical methods like UV-visible, ¹H and ¹³C-NMR, FT-IR, mass spectrometry, elemental analysis, thermal analysis, and molar conductivity. Structural investigation of crystalline AHB was also performed by single-crystal X-ray crystallography. Based on the structural analysis, an octahedral geometry for the Cr(III) complex, square planar geometry for the Co(II) complex, tetrahedral geometry for the Zn(II) complex, and square pyramidal geometry for the VO(IV) complex were proposed. The synthesized bidentate ligand was found to be coordinated with the metal ions via nitrogen and oxygen donor atoms. All of the synthesized compounds were found to be non-electrolytic. The thermogravimetric analysis demonstrated the thermally stable nature of complexes, more than the ligand. The hypoglycemic potential of the compounds was estimated by in vitro inhibitory activities of α-amylase and α-glucosidase enzymes. The tested ligand-AHB was found to be relatively inactive toward both enzymes, while its metal complexes were found to be good α-glucosidase inhibitors as compared to α-amylase inhibitors. Among all prepared compounds, the Zn(II) complex was found to be a good α-glucosidase inhibitor comparable to the standard (acarbose), while other complexes showed a moderate inhibition of α-glucosidase. Both Cr(III) and Co(II) complexes were found to be effective α-amylase inhibitors. Based on the current findings, it can be anticipated that the synthesized compounds can be tried as effective therapeutic agents to cure diabetes mellitus.