Computational study concerning some ۳-Chromonyl-۲-oxo-propionic acid derivatives and their inhibitory effects on HIV-۱ integrase activity

Deprotonation of ۳-Chromonyl-۲-oxo-propionic acid and its derivatives have been considered by quantum mechanical calculations. Results indicate that deprotonation energies decrease by the electron-withdrawing (EW) substituents and increase by the electron-donating (ED) ones. Also, energy data and results of atoms in molecules (AIM) analysis show that because of intramolecular hydrogen bonding interactions deprotonation of the derivatives with EW substituents are easier than those with ED ones. In all derivatives, deprotonations are almost negligible which predict similar pharmacophore properties for all of them. The inhibitory effects of these molecules on HIV۱ integrase were investigated and with respect to the results of molecular docking, some of derivatives are not only effective inhibitors, but they can also use as a replacement for ۳-Chromonyl-۲-oxo-propionic acid, especially (۶-Benzylchromone-۳-yl)-۲-oxo-propionic acid (CHO-C۶H۵ ) which is the best one. Also, orientation and interaction energies of this molecule are estimated and suitable interactions with LYS۱۵۶, and LYS۱۵۹ amino acids, and Mg۲+ cation are obtained.

Keywords:

deprotonation , AIM , intramolecular hydrogen bonding , HIV-۱ integrase inhibitors , molecular docking