An In Silico Study of Examining Bioactive Compounds from Azadirachta indica Juss. (Neem) as Potential Death Receptor 5 Inductor in Hepatoma Cells

Abstract

Hepatocellular carcinoma is a disease that occurs due to the uncontrolled growth of abnormal hepatocytes. While cancer cells will not die by itself, due to resistance to death receptors 5 (DR5)-mediated apoptosis. This study is aimed to investigate Azadirachta indica Juss. leaves compound, such as gedunin and nimbolide, in binding DR5 and stimulated the TNF-related apoptosis inducing ligand (TRAIL), native ligand binding to DR5, which has a role of pro-apoptotic by docking simulation. The ligand and protein preparations were done using Discovery Studio 2016 and Hex 8.0.0 for docking. Visualization was done using Discovery Studio 2016. The docking studies revealed that nimbolide has a lower binding energy with the DR5-TRAIL complex than gedunin. According to the findings, nimbolide is a more effective DR5-TRAIL binding inducer than gedunin and has a higher binding affinity for DR5-TRAIL. This interaction has the potential to significantly reduce DR5-TRAIL binding resistance. Nimbolide and gedunin can be considered as drugs that can sensitize TRAIL binding to DR5 and increase the activation of one of hepar cancers signaling apoptosis pathways. Key words: Azadirachta indica Juss., Cancer, Death receptor 5, Apoptosis, In silico