The physicochemical properties and tyrosinase inhibitory activity of ectoine and its analogues: A theoretical study

Protonation, deprotonation, and proton transfer were considered in ectoine (ECT) and some of its derivatives in the gas phase and solution media by the quantum mechanical calculations. The results of present study help to understand the activity of mentioned compounds as osmolytes, which are also important in water activity and osmotic pressure within a cell. Proton diffuses through the water solvent, covers the distance between the acidic and basic groups, and leads to the protonation of basic group. The deprotonation of NH group is often easier than COOH, because of intramolecular H-bond interactions in the anionic forms. The protonation of N atom is easier than the deprotonation of COOH and NH groups in all compounds with respect to the energy data, results of atoms in molecules (AIM), and molecular electrostatic potential (MEP) analyses. The proton transfer from NH to N is favorable in solution media, acidic and basic environments which is in agreement with the high tendency of NH group and N atom in deprotonation and protonation, respectively. Results indicate that protonation, deprotonation, and proton transfer are almost the same in all compounds and lead to the same biological activities. In addition, the inhibitory activity of compounds on tyrosinase enzyme was studied using the results of molecular docking. The proper orientation of PO3H2 group in the binding pocket causes suitable interactions with HIS244, GLU256, and ASN260 amino acids. Thus, it seems that the highest inhibitory activity corresponds to the compound with the-CH2-PO3H2 substituent. (C) 2018 Elsevier B.V. All rights reserved.