In silico Pharmacokinetics and Molecular Docking Studies of Lead Compounds Derived from Diospyros Mespiliformis

Pharmacokinetics and toxicity profile along with efficacy are the major determinants for successful drug development. This study was carried out to determine the pharmacokinetic profile, potential biological activities and toxicity of diospyrin, lupeol and plumbagin using in silico approaches. The Swiss ADME tool was used to calculate the molecular properties of the ligands based on Lipinski’s rule of five (5).All ligands in the present study satisfied the rule. Using the Swiss ADME tool, the pharmacokinetic profile of the compounds was evaluated. Protox-II server was used to predict the organ toxicities and toxicological end points of the ligands and their LD50. Plumbagin is found to have both mutagenicity and carcinogenicity. Lupeol and diospyrin are reported to be immunotoxic. Lupeol has LD50 of 2000mg/kg. Diospyrin and plumbagin have 16mg/kg. Swiss target prediction server was used to identify the various potential target. The target prediction suggests that plumbagin and lupeol have high preference for Microtubule-associated protein tau (MAPT). The best target for diospyrin was Aurora kinase A. Molecular docking study was conducted using AutoDock vina in The Python Prescription (PyRx) 0.8 virtual screening tool. Plumbagin and lupeol were docked against Microtubule associated protein tau. The dockings scores based on binding energy were; plumbagin -33.8 (kcal/mole) and lupeol -44.7 (kcal/mole). Diospyrin showed a binding energy of -10.7 (kcal/mole) against Aurora A kinase. Results in this study suggest that diospyrin may serve as an important aurora kinase inhibitor while lupeol and plumbagin may be useful in treatment of Alzheimer’s disease.