Exploring Schiff bases derived from 4-(diethylamino)salicylaldehyde and their copper(II) complexes as antidiabetes and antioxidant agents: Structural elucidation, DFT computational and in vitro studies

A series of three Schiff base ligands and their metal complexes with copper(II) have been prepared. The ligands are (E)-5-(diethylamino)-2-(((2,6-dimethylphenyl)imino)methyl)phenol (C1), (E)-5-(diethylamino)-2-(((2,6-diisopropylphenyl)imino)methyl)phenol (C2) and (E)-5-(diethylamino)-2-((mesitylimino)methyl)phenol (C3). They were reacted with copper(II) nitrate trihydrate (Cu(NO3)2 & sdot;3H2O) to give [Cu(C1)2] (1), [Cu(C2)2] (2), and [Cu(C3)2] (3). All the synthesized compounds were elucidated by exploring mass, FT-IR, UV-Vis, and NMR (1H & 13 C) spectroscopic techniques while elemental analysis was carried out to affirm their purity. The paramagnetic nature of 1 , 2 and 3 was established using EPR spectra. The molecular structure of C1 and C2 were further confirmed using single crystal X-ray crystallography. The bond lengths of C7-N1, C7-C8 and C8-C9 obtained from structural analysis for C1 and C2 depicted their enol-tautomeric characteristic form. Quantum chemical calculations revealed that all the compounds have small energy band gaps (Delta E) with complex 2 having the lowest Delta E of 0.21 eV. The antidiabetes potential of the compounds were evaluated using alpha-amylase and alpha-glucosidase assays. Compound C1 with an IC50 value of 0.11 mM, displayed almost equal alpha-amylase inhibition capacity as the one for acarbose (reference drug) with IC50 value of 0.07 mM. Compounds C3 a nd 2 displayed good alpha-glucosidase inhibition activities with IC50 value of 0.05 mM and 0.19 mM respectively. The synthesized compounds displayed moderate to excellent antioxidant potential. Complex 1 and the ligands (C1-C3) have lower IC50 value than quercetin (reference drug) for nitric oxide assay. Estimated physicochemical parameters revealed that C1 and C3 fell within the threshold of Lipinski's rule of five (Ro5) while C2 as well as complex 1 - 3 deviates minimally.