Lantadenes Targeting NF-ΚB in Cancer: Molecular Docking and ADMET Predictions

Abstract

Natural products and their scaffolds encompasses an array of molecular entities as starting points for drug designing and discovery. In the past two decades, phytochemically driven Lantadenes and their modified analogues have attracted lots of attention due to their tumor necrosis factor-α induced nuclear factor-kappa B inhibition and consequently their promising anticancer potential. Earlier reports described the synthesis of esters at C-3 and C-22 of pentacyclic triterpenoid Lantadene, and their evaluation to inhibit tumor necrosis factor-α induced nuclear factor-kappa B along with cytotoxicity against A549 lung cancer cells. In the modern drug discovery process, molecular docking have become an integral part of drug design. Combination of computational platforms and experimental strategies have allowed many successful stories in the discovery of new structure-based or mechanism drugs. Thus as a continuation of our research concerning Lantadenes and their significance, present study has been undertaken to predict binding mode, pharmacokinetic and drug likeness using Vlife MDS Biopredicta and ADMETlab tools. In silico inspired grip docking approach was utilized to estimate binding interactions of all the optimized Lantadenes and their modified ester against nuclear factor-kappa B receptor (PDB ID: 1LE9). In addition, all the compounds were screened for pharmacokinetic profile and drug likeness as an important consideration for the selection of compounds with desirable prosperities using ADMETlab tools. Ligand-receptor analysis revealed Lantadene parent nuclei and their modified analogues as potent inhibitors of nuclear factor-kappa B receptor based on binding energy (-21.16 to -42.56 kcal/mol), number of interactions and bond length. Furthermore, most of the analogues were found to have good ADMET profiles. Cumulative computational analyses provided the lead Lantadene analogue 10 and can be considered as a potential candidate for detailed mechanistic studies against lung cancer.