In-silico evaluation of bioactive compounds from natural sources targeting NIK and NF-κB pathways for chronic prostatitis therapy and ADMET profile analysis

Abstract

Inflammation, cancer and a variety of human disorders are connected with NF-ΚB and NF-κB -­­­­­inducing kinase light-chain-enhancer of activated b cells increased expression in the biological framework. The NF-κB and NIK cascades vital components may control the relocation as well as stimulation of the NF-κB transcription factor along with NIK. The current work focuses on active site ­­­­­­­­analysis as well as molecular docking investigations of NF-κB and NIK pathway key components. The natural chemicals employed as ligands in this docking investigation are Guggulsterone Z and Withaferin A. The present study focused on comparative docking studies on drug target proteins using separate ligands. The current study shed information on the binding capacities and interactions of components found in the oleoresin of Ashwagandha and Guggul plants with the active sites of NFkB and NIK. The molecular docking studies predicted an improved interaction between NFkB NIK, and the bioactive content of Ashwagandha (Withaferin A) and Guggul (Guggulsterone Z (GZ)) with binding energies of -7.5, -8.8, -7.1, and -8.2 kcal/mol, confirming the coexistence of both ligands at different binding sites of the metabolising enzymes. Furthermore, the ADMET and drug-likeness ratings were shown to be beneath the normal range for water solubility, Caco-2 permeation, human intestinal absorption (HIA), and blood-brain barrier (Absorption) and exhibited negative cancer-causing consequences.