Anti-Tuberculosis Activity in Punica granatum: In silico Validation and Identification of Lead Molecules

Abstract

Discovery of novel drug against tuberculosis is inevitable since resistant bacterial strains are evolved against existing drugs and rapidly active single drug in short period is necessary for effective treatment. When compared to synthetic drugs, natural drugs particularly phytochemicals induce less side effects and long term stability. In Indian traditional medicine, several plant species have been used for treating tuberculosis and each plant species contains a plethora of phytochemicals. The efficacy of such treatment system and identification of the phytochemical with drug activity from plants has been seldom investigated scientifically. In this backdrop, the authors have validated the efficacy of anti-tuberculosis activity and identified lead molecule from a widely used plant species against several disease including tuberculosis, viz Punica granatum L. The four promising target proteins viz mycolyltransferase antigen protein 85C involved in cord factor synthesis, filamentous temperature sensitive protein Z involved in bacterial cell division, pantothenate kinase involved in co-enzyme A pathway and decaprenylphosphoryl β-D-ribofuranose-2 epimerase involved in the synthesis of virulent factor arabinan were docked with 243 phytochemicals derived from Punica granatum. The docked molecules having binding energy ≤-6 kcal/ mol were considered as active/hit molecules. The docked results showed that out of 243 phytochemicals, 126 have inhibitory activity on all selected target proteins. Further docking study using Glide and absorption, distribution, metabolism, excretion and toxicity studies revealed that the compound derived from the flowers, pomegranate can be recommended as the best lead compound against tuberculosis.