Electrochemical and Molecular Docking Studies on DNA, HSA and BSA Bindings and in Silico Physicochemical Properties of (E)-1 and (E)-1

Abstract

The binding interactions of (E)-1-((2,4-dichlorophenylimino)methyl)naphthalen-2-ol (DCPIMN) and (E)-1-((2-chloro-4-nitrophenylimino)methyl)naphthalen-2-ol (CNPIMN) with some biomolecules, namely, calf thymus DNA (ct-DNA) and serum albumins (HSA and BSA) were investigated by square-wave voltammetry (SWV) at physiological pH of 7.40. Also, the absorption, distribution, metabolism and excretion (ADME) profiles of DCPIMN and CNPIMN were reported. DCPIMN had an irreversible voltammetric peak at -1.352 V on the mercury electrode at pH 7.40. However, in physiological pH, electrochemical experiments revealed that CNPIMN showed two irreversible cathodic peaks owing to reductions of nitro and azomethine moieties, respectively. The variations in the current and potential values of reduction signals of DCPIMN and CNPIMN with adding of different concentrations of these biomolecules (BMs) were followed. The voltammetric experiments showed that although DCPIMN interacted with these BMs, CNPIMN only interacted with HSA. The binding constants (K) of these 1 : 1 interactions were calculated from electrochemical data. These K values showed that the binding strength of BSA to DCPIMN is stronger than those of HSA and ct-DNA compounds. Moreover, CNPIMN binds more strongly to HSA than DCPIMN. On the other hand, the molecular docking studies of DCPIMN and CNPIMN were carried out to evaluate their theoretical binding affinities. The binding affinity (BA) of BSA (-8.9 kcal/mol) with DCPIMN is higher than those of A-DNA, B-DNA and HSA. In addition, the BA value of HSA with CNPIMN is also greater than that of its interaction with DCPIMN. From the molecular docking results, it was found that there was a hydrogen bond between -NO2 group of CNPIMN and ARG117 residue of HSA. Finally, pharmacokinetic properties of these Schiff bases exhibited that DCPIMN has the capability of blood-brain barrier (BBB) penetration; however, CNPIMN does not have this feature.