The electrochemical properties and PIM1 kinase enzyme inhibition of some 2-(hydroxy phenyl amino) naphthalene-1,4-dione derivatives

Abstract

Abstract In the present work, the electrochemical properties of some 2-(hydroxy phenyl amino) naphthalene-1,4-dione derivatives (HPAN-X), and the effects of π-stacking interactions on the mentioned properties were estimated using the quantum mechanical calculations. All substituents enhance the π-stacking interactions in the HPAN-X⋯C6H6 complexes, where changes are larger by electron-withdrawing groups. The π-stacking interactions often decrease the reduction potentials (E0red), the energy gap between natural frontier molecular orbitals LUMO and HOMO, and also decrease the electron affinities (EA), vertical (VEA), adiabatic (AEA), and zero point-corrected electron affinities (EAZPE) of compounds. The parameters of linear relationships between EA-AEA, EA-VEA, AEA-VEA, and EA-EAZPE pairs are also presented for compounds and complexes. Rational relationships are observed between the values of E0red and Hammett constants of substituents. The effects of π-stacking interactions on electrochemical properties are discussed on the base of results of the atoms in molecules (AIM) and natural bond orbital (NBO) analyses. In addition, the molecular docking were used to study the modes of interaction of the HPAN-X with PIM1 kinase active site. Using both softwares, the docking results present 2HPAN-NH2 as the best inhibitor, where the π- staking interaction with Phe187 amino acid residue substantially affects the ability of compound to inhibit the active site of PIM1 kinase.