Computational analysis of natural compounds targeted for NICD of notch pathway in hepatocellular carcinoma

Abstract

Therapeutic drugs are required to fight against Hepatocellular carcinoma (HCC), which is one of the prominent cancer types and is considered the world's second leading cause of death related to cancer. HCC is caused by chronic usage of alcohol, obesity, hepatitis virus etc. Currently, the chemotherapeutics drugs available possess severe side effects and face multi-drug resistance due to which the mortality rate is high. The normal liver shows lower expression of notch receptors in comparison to HCC patients where overexpression of notch receptors is observed in the patient’s liver. The present study is based on screening natural compound databases using structure-based virtual screening to find compounds with the capability to inhibit the expression of Notch signaling pathway. 7929 compounds from three natural compound databases (NANPDB, EANPDB, and SANCDB) were subjected to LibDock succeeded by ADME and toxicity prediction using Biovia Discovery Studio Suite. To observe the binding system, molecular docking was performed between the natural compounds and the Notch intracellular domain (target molecule). The computational analysis resulted in a novel natural compound i.e., 5-(2′',3′'-epoxy-3′'-methylbutyl)-3-(3′-hydroxy-3′-methyl-1′-acetyloxy-but-2′-yl)indole. In silico ADMET analysis showed that this compound had good absorption levels with minimal toxic effects. In future, this compound can be utilized as a lead molecule for the development of an anti-HCC medication.