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

Abstract

• Three novel Schiff bases as well as their copper(II) complexes have been successfully synthesized and characterized. • Crystal structure analysis revealed the enol-tautomeric characteristics in two ligands. • Besides complex 3 , all the compounds exhibited moderate to good antidiabetes potential. • Complex 3 with least IC 50 value displayed highest DPPH free radical scavenging ability. • All the ligands and complex 1 show excellent NO mopping ability and are even superior to quercetin. • Estimated physicochemical and pharmacokinetic parameters of the ligands C1 – C3 fell within the threshold of Lipinski’s Ro5. 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(NO 3 ) 2 ·3H 2 O) 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 ( 1 H & 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 (ΔE) with complex 2 having the lowest ΔE of 0.21 eV. The antidiabetes potential of the compounds were evaluated using α-amylase and α-glucosidase assays. Compound C1 with an IC 50 value of 0.11 mM, displayed almost equal α-amylase inhibition capacity as the one for acarbose (reference drug) with IC 50 value of 0.07 mM. Compounds C3 a nd 2 displayed good α-glucosidase inhibition activities with IC 50 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 IC 50 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.

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