In silico Computation of Theoretical Physicochemical Properties and Pharmacokinetic Profiles of Some Novel Substituted Amodiaquine Based Compounds

Abstract

Based on our previous molecular docking research studies of amodiaquine-based compounds and establishment of 3 potent inhibitors (8, 9, and 21), in the present study, a continued effort was presented where physicochemical parameters such as lipophilicity (log P), molar refractivity (cLogP), heat of formation (at 250 Kcal/mol), Gibb’s free energy ( KJ/mol), bond energy (Kcal/mol), dipole-dipole energy (Kcal/mol), stretch energy (Kcal/mol), torsion energy (Kcal/mol), and total energy (Kcal/mol) using the ChemDraw 3D 8.0 software for 25 compounds. The pharmacokinetic parameters such as Solute Total SASA, QP log P for octanol/gas, Jorgensen Rule of 3 Violations, Solute Dipole Moment (D), Maximum Transdermal Transport Rate (Jm), Number of Primary Metabolites, Qualitative Model for H.O.A., Solute as Donor - Hydrogen Bonds, Solute Molecular Weight (MW), Apparent MDCK (nm/sec), Solute Carbon Pi SASA, QP log S for aqueous solubility, % Human Oral Absorption (±20%), Solute Weakly Polar SASA, QP log Kp for skin permeability, Solute Hydrophobic SASA, Apparent Caco-2 (nm/sec), QP log BB for brain/blood, Solute Hydrophilic SASA, Predicted CNS Activity (-- to ++), QP log P for water/gas, Solute vdW Polar SA (PSA), Lipinski Rule of 5 Violations, Solute Molecular Volume (A^3), QP log P for octanol/water, Solute as Acceptor – H-Bonds, QP log S, Solute Globularity (Sphere = 1), QP log K - Serum Protein Binding, Solute Ionization Potential (eV), HERGK+ Channel Blockage, QP Polarizability (Angstroms^3), and Solute Electron Affinity (eV) were determined using the Schrodinger Maestro 9.1 software for 3 best inhibitors.