In-Silico Analysis of Hydroxychavicol and Ursolic Acid for Targeting ICPs Involved in NSCLC

Lung cancer is the second most fatal cancer type with 85 % of the cases accounting for Non-Small Cell Lung Carcinoma (NSCLC) and instances of maximum subtype Adenocarcinoma. Adenocarcinoma initiates in bronchial mucus-secreting glands and spreads to the lung periphery. Surgery, chemotherapy, and radiation therapy are currently available therapies. However, tumors resist these therapies by evolving immune escape mechanisms, like immune checkpoint signaling. Hence, a new therapeutic approach based on activating patients’ immune cells is of interest. Two phytoconstituents, Hydroxychavicol and Ursolic acid were evaluated for potential pharmacokinetic properties using the SwissADME web tool. They were docked using Molecular Operating Environment (MOE) with six ICPs to identify their potential as novel checkpoint blockers. The results showed a good drug-like nature of both the phytoconstituents. Their docking scores and the predicted binding sites are comparable to the existing therapeutic candidates in the market and clinical trials. This indicates their significant binding affinity towards ICPs. Ionic, Hydrogen bonding, and Van der Waals interactions were involved in binding. Promising targets related to T-cell exhaustion have been revealed for both the phytoconstituents. This analysis may enable the discovery of plant-derived potential immune checkpoint blockers that can impede immune suppression in NSCLC treatment.