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

Segun D Oladipo; Robert C Luckay; Kolawole A Olofinsan; Vincent A Obakachi; Sizwe J Zamisa; Adesola A Adeleke; Abosede A Badeji; Segun A Ogundare; Blassan P George

doi:10.1016/j.heliyon.2023.e23174

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

Heliyon. 2023 Dec 2;10(1):e23174. doi: 10.1016/j.heliyon.2023.e23174. eCollection 2024 Jan 15.

Authors

Segun D Oladipo^{1

2}, Robert C Luckay¹, Kolawole A Olofinsan³, Vincent A Obakachi⁴, Sizwe J Zamisa⁵, Adesola A Adeleke², Abosede A Badeji⁶, Segun A Ogundare², Blassan P George³

Affiliations

¹ Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa.
² Department of Chemical Sciences, Olabisi Onabanjo University, P.M.B 2002, Ago-Iwoye, Nigeria.
³ Laser Research Centre, Faculty of Health Sciences, University of Johannesburg, P.O Box 17011, Doornfontein, 2028, South Africa.
⁴ Department of Pharmaceutical Chemistry, Discipline of Pharmaceutical Sciences, College of Health Sciences, University of Kwazulu-Natal, Durban, South Africa.
⁵ School of Chemistry and Physics, Westville Campus, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa.
⁶ Department of Chemical Sciences, Tai Solarin University of Education, Ijagun, Ogun State, Nigeria.

Abstract

Three Schiff bases were synthesised by the condensation reaction between 2-napthaldehyde and aromatic amines to afford (E)-N-mesityl-1-(naphthalen-2-yl)methanimine (L1), (E)-N-(2,6-dimethylphenyl)-1-(naphthalen-2-yl)methanimine (L2) and (E)-N-(2,6-diisopropylphenyl)-1-(naphthalen-2-yl)methanimine (L3). The synthesised compounds were characterised using UV-visible, NMR (¹³C & ¹H), 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 L2 and L3, respectively. Of all the various intermolecular contacts, H⋯H interactions contributed mostly towards the Hirshfeld surfaces of both L2 (58.7 %) and L3 (69.7 %). Quantum chemical descriptors of L1 - L3 were determined using Density Functional Theory (DFT) and the results obtained showed that the energy band gap (ΔE) for L1, L2 and L3 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 L1 showed very promising antidiabetic activities with IC₅₀ 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. In-silico studies showed that L1 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 L1 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 L1 as well as L3 having IC₅₀ values of 70.91 and 91.21 μg/mL respectively for NO scavenging activities assay, which comparatively outshined acarbose (reference drug) with IC₅₀ value of 109.95 μg/mL. Pharmacology and pharmacokinetics approximations of L1 - L3 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.

Keywords: Antidiabetes; Antioxidant; Crystal structure; Hirshfeld analysis; Schiff bases.