Molecular modeling and DFT studies of diazenylphenyl derivatives as a potential HBV and HCV antiviral agents

Abstract

The need for novel antiviral drug particularly for hepatitis B (HBV) and C (HCV) virus cannot be over emphasized hence, this work focuses on the stability and intermolecular interaction of three diazenylphenyl compounds; 5-((E)-(4-((E)-(3-hydroxy-nitrosonaphthalen-1-yl)diazinyl)phenyl)diazinyl)-3,8a-dihydroquinolin-8-ol, (Z)-4-(E-(4-(E)-(2,4-dihydroxyphenyl)phenyl)diazinyl-2-(hydroxyamino)-4a,8a-dihyroapthalen-1(2H)-one, and 4-((E)-(4-((E)-(2-hydroxy-3-nitrosophenyl)diazenyl)phenyl)diazenyl)-4a,8a-dihydronaphthalen-1(4H)-one depicted as A, B and C respectively. We have performed a comprehensive quantum computational study to ascertain the drug likeness of the titled molecules. Interestingly, Compound C was found to be the most stable compound compared to A and B. In the Density of state (DOS) studies, hydrogen was observed to have the highest peak in the antibonding region whereas carbon has the highest values at the bonding molecular orbitals. Compound C have the highest second order perturbation energies. The molecular dynamics simulation of the individual molecules indicate that compound B + 4MWF complex has the highest binding energy than other complexes and the RMSD values indicate that the targeted K7F, 6CWT, 4MWF and 5YAX proteins are more conformationally stable when bound with compound B. Antiviral property of the titled molecules was investigated by docking with the selected viral proteins. The studied compounds were observed to have the highest binding affinity compared to Telbivudine and Sofosbuvir which were used as standard drugs.