Investigating the potential of fluorinated hydrazide and hydrazones as inhibitors of COVID-19 main protease using molecular docking and DFT calculations

Abstract

The enhanced biological activity of fluorine-containing compounds has led to their exploration as possible drug candidates against viral diseases. In this study, fluorine-containing hydrazide and hydrazones derived from 1- cyclopropyl-6,7-difluoro-8-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid were investigated for their potential as drug candidates against COVID-19 via computational methods comprising DFT studies, molecular docking, and absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis. The electronic properties of the compounds were computed using DFT analysis, with the energy gap of the compounds ranging from 3.77 eV for FHI to 4.57 eV for FHA. The chemical hardness ranged from 1.89 eV for FHI to 2.04 for FHA, and electrophilicity index values ranged from 3.16 for FHD to 3.65 for FHJ, depicting the electrophilic nature of all the compounds. The docking results showed that the fluorinated hydrazide and hydrazones exhibited moderate binding energies, higher than those of chloroquine but lower than the binding energy of remdesivir, frontline drugs used in dealing with COVID-19. Using Discovery Studio, visualizations revealed that hydrogen bonding, alkyl interaction, pi-sulphur interaction, halogen interaction, carbon-hydrogen interaction, and Pi-Donor hydrogen interaction were responsible for the binding energy values. The ADMET test showed that all the compounds could serve as potential inhibitors of COVID-19 as they adhere to Lipinski and Veber's rules.