Molecular Docking, Drug-Likeness, Pharmacokinetics Properties Prediction and DFT Calculation of Some Dehydroandrogrhapholide and Andrographolides Derivatives as Anti-Hepatitis B Virus Agents

Abstract

Hepatitis B is a liver infection caused by the hepatitis B virus which usually spread through contact with blood, semen or other body fluids of an infected person. If not treated with caution, hepatitis B virus would gradually grow into a more severe state which results in scarring of the liver, abnormal functionality of the liver and in due time, liver cancer or cirrhosis. In this research, molecular docking studies was carried out on dehydroandrographolide and andrographolide derivatives as anti-hepatitis B virus agents against HBV target (Nucleoside diphosphate kinase) with the pdb ID: 4C6A. The drug-likeness and pharmacokinetic properties of the investigated molecules were also studied. The molecular docking study carried out on the anti-hepatitis B virus agents has explored their theoretical binding affinities with the active sites of the HBV target (Nucleoside diphosphate kinase) in a range of -112.23 to -175.17kcal/mol. Compounds A9 has the highest binding affinity of -175.17kcal/mol out of the 20 dehydroandrographolide and andrographolide derivatives investigated. It formed 4 conventional hydrogen bond interactions with LYS16 (2.77 Å), TYR56 (1.96 Å), ARG109 (3.04 Å) and GLY123 (2.43 Å) amino acid residues. It also formed the carbon-hydrogen bond with LYS16 (2.62 Å), ARG92 (2.62 Å) and ARG92 (2.75 Å) amino acid residues, respectively. It further formed Alkyl hydrophobic bond interaction with ARG92 (4.49 Å), ILE95 (5.18 Å), LEU68 (3.85 Å) and Pi-Alkyl hydrophobic with TYR56 (4.58 Å), HIS59 (5.18 Å), ALA14 (4.82) amino acid residues, respectively. The drug likeness and pharmacokinetics properties prediction performed showed that the studied compounds including the best lead compounds were drug-like in nature with good pharmacokinetics properties and they all have bioavailability score of 0.55, respectively. The DFT studies revealed that compound 2 and 8 among the best five compounds are more reactive having lower energy band gap of 4.3eV, respectively.