Antidiabetes and antioxidant potential of Schiff bases derived from 2-naphthaldehye and substituted aromatic amines: Synthesis, crystal structure, Hirshfeld surface analysis, computational, and studies.

Three Schiff bases were synthesised by the condensation reaction between 2-napthaldehyde and aromatic amines to afford -mesityl-1-(naphthalen-2-yl)methanimine (), ()--(2,6-dimethylphenyl)-1-(naphthalen-2-yl)methanimine () and -(2,6-diisopropylphenyl)-1-(naphthalen-2-yl)methanimine (). The synthesised compounds were characterised using UV-visible, NMR (C & H), and Fourier transform infrared spectroscopic methods while their purity was ascertained by elemental analysis. Structural analysis revealed that the naphthalene ring is almost coplanar with the imine functional group as evident by C1-C10-C11-N1 torsion angles of 176.4(2)° and 179.4(1)° in and , respectively. Of all the various intermolecular contacts, H⋯H interactions contributed mostly towards the Hirshfeld surfaces of both (58.7 %) and (69.7 %). Quantum chemical descriptors of - were determined using Density Functional Theory (DFT) and the results obtained showed that the energy band gap (ΔE) for , and are 3.872, 4.023 and 4.004 eV respectively. The antidiabetic potential of the three compounds were studied using α-amylase and α-glucosidase assay. Compound showed very promising antidiabetic activities with IC values of 58.85 μg/mL and 57.60 μg/mL while the reference drug (Acarbose) had 405.84 μg/mL and 35.69 μg/mL for α-amylase and α-glucosidase respectively. studies showed that docking score as well as binding energies are higher than that of acarbose, which are recognized inhibitors of α-amylase together with α-glucosidase. Further insight from the RMSF, RMSD and RoG analysis predicted that, throughout the simulation showcased evident influence on the structural stability of α-amylase. The antioxidant potential of the compounds was carried out using nitric oxide (NO), ferric reducing ability power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. The compounds exhibited good to fairly antioxidant properties with as well as having IC values of 70.91 and 91.21 μg/mL respectively for NO scavenging activities assay, which comparatively outshined acarbose (reference drug) with IC value of 109.95 μg/mL. Pharmacology and pharmacokinetics approximations of - showed minimal violation of Lipinski's Ro5 and this projects them to be less toxic and orally bioavailable as potential templates for the design of therapeutics with antioxidant and antidiabetic activities.